[{"publisher":"American Chemical Society ","month":"05","abstract":[{"text":"Additional analyses of the trajectories","lang":"eng"}],"oa_version":"Published Version","date_published":"2020-05-20T00:00:00Z","doi":"10.1021/jacs.9b13450.s001","related_material":{"record":[{"id":"8040","status":"public","relation":"used_in_publication"}]},"date_created":"2021-07-23T12:02:39Z","year":"2020","day":"20","type":"research_data_reference","status":"public","_id":"9713","author":[{"first_name":"Chitrak","last_name":"Gupta","full_name":"Gupta, Chitrak"},{"last_name":"Khaniya","full_name":"Khaniya, Umesh","first_name":"Umesh"},{"last_name":"Chan","full_name":"Chan, Chun Kit","first_name":"Chun Kit"},{"last_name":"Dehez","full_name":"Dehez, Francois","first_name":"Francois"},{"last_name":"Shekhar","full_name":"Shekhar, Mrinal","first_name":"Mrinal"},{"full_name":"Gunner, M.R.","last_name":"Gunner","first_name":"M.R."},{"id":"338D39FE-F248-11E8-B48F-1D18A9856A87","first_name":"Leonid A","last_name":"Sazanov","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A"},{"full_name":"Chipot, Christophe","last_name":"Chipot","first_name":"Christophe"},{"first_name":"Abhishek","full_name":"Singharoy, Abhishek","last_name":"Singharoy"}],"article_processing_charge":"No","department":[{"_id":"LeSa"}],"title":"Supporting information","date_updated":"2023-08-22T07:49:38Z","citation":{"mla":"Gupta, Chitrak, et al. Supporting Information. American Chemical Society , 2020, doi:10.1021/jacs.9b13450.s001.","short":"C. Gupta, U. Khaniya, C.K. Chan, F. Dehez, M. Shekhar, M.R. Gunner, L.A. Sazanov, C. Chipot, A. Singharoy, (2020).","ieee":"C. Gupta et al., “Supporting information.” American Chemical Society , 2020.","apa":"Gupta, C., Khaniya, U., Chan, C. K., Dehez, F., Shekhar, M., Gunner, M. R., … Singharoy, A. (2020). Supporting information. American Chemical Society . https://doi.org/10.1021/jacs.9b13450.s001","ama":"Gupta C, Khaniya U, Chan CK, et al. Supporting information. 2020. doi:10.1021/jacs.9b13450.s001","chicago":"Gupta, Chitrak, Umesh Khaniya, Chun Kit Chan, Francois Dehez, Mrinal Shekhar, M.R. Gunner, Leonid A Sazanov, Christophe Chipot, and Abhishek Singharoy. “Supporting Information.” American Chemical Society , 2020. https://doi.org/10.1021/jacs.9b13450.s001.","ista":"Gupta C, Khaniya U, Chan CK, Dehez F, Shekhar M, Gunner MR, Sazanov LA, Chipot C, Singharoy A. 2020. Supporting information, American Chemical Society , 10.1021/jacs.9b13450.s001."},"user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf"},{"_id":"9878","type":"research_data_reference","status":"public","date_updated":"2023-08-22T07:49:38Z","citation":{"apa":"Gupta, C., Khaniya, U., Chan, C. K., Dehez, F., Shekhar, M., Gunner, M. R., … Singharoy, A. (2020). Movies. American Chemical Society. https://doi.org/10.1021/jacs.9b13450.s002","ama":"Gupta C, Khaniya U, Chan CK, et al. Movies. 2020. doi:10.1021/jacs.9b13450.s002","short":"C. Gupta, U. Khaniya, C.K. Chan, F. Dehez, M. Shekhar, M.R. Gunner, L.A. Sazanov, C. Chipot, A. Singharoy, (2020).","ieee":"C. Gupta et al., “Movies.” American Chemical Society, 2020.","mla":"Gupta, Chitrak, et al. Movies. American Chemical Society, 2020, doi:10.1021/jacs.9b13450.s002.","ista":"Gupta C, Khaniya U, Chan CK, Dehez F, Shekhar M, Gunner MR, Sazanov LA, Chipot C, Singharoy A. 2020. Movies, American Chemical Society, 10.1021/jacs.9b13450.s002.","chicago":"Gupta, Chitrak, Umesh Khaniya, Chun Kit Chan, Francois Dehez, Mrinal Shekhar, M.R. Gunner, Leonid A Sazanov, Christophe Chipot, and Abhishek Singharoy. “Movies.” American Chemical Society, 2020. https://doi.org/10.1021/jacs.9b13450.s002."},"user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","author":[{"full_name":"Gupta, Chitrak","last_name":"Gupta","first_name":"Chitrak"},{"full_name":"Khaniya, Umesh","last_name":"Khaniya","first_name":"Umesh"},{"full_name":"Chan, Chun Kit","last_name":"Chan","first_name":"Chun Kit"},{"full_name":"Dehez, Francois","last_name":"Dehez","first_name":"Francois"},{"last_name":"Shekhar","full_name":"Shekhar, Mrinal","first_name":"Mrinal"},{"full_name":"Gunner, M.R.","last_name":"Gunner","first_name":"M.R."},{"first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","last_name":"Sazanov","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A"},{"first_name":"Christophe","full_name":"Chipot, Christophe","last_name":"Chipot"},{"full_name":"Singharoy, Abhishek","last_name":"Singharoy","first_name":"Abhishek"}],"article_processing_charge":"No","title":"Movies","department":[{"_id":"LeSa"}],"oa_version":"Published Version","publisher":"American Chemical Society","month":"05","year":"2020","day":"20","date_published":"2020-05-20T00:00:00Z","related_material":{"record":[{"status":"public","id":"8040","relation":"used_in_publication"}]},"doi":"10.1021/jacs.9b13450.s002","date_created":"2021-08-11T09:18:54Z"},{"article_number":"4135","citation":{"apa":"Gutierrez-Fernandez, J., Kaszuba, K., Minhas, G. S., Baradaran, R., Tambalo, M., Gallagher, D. T., & Sazanov, L. A. (2020). Key role of quinone in the mechanism of respiratory complex I. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-020-17957-0","ama":"Gutierrez-Fernandez J, Kaszuba K, Minhas GS, et al. Key role of quinone in the mechanism of respiratory complex I. Nature Communications. 2020;11(1). doi:10.1038/s41467-020-17957-0","short":"J. Gutierrez-Fernandez, K. Kaszuba, G.S. Minhas, R. Baradaran, M. Tambalo, D.T. Gallagher, L.A. Sazanov, Nature Communications 11 (2020).","ieee":"J. Gutierrez-Fernandez et al., “Key role of quinone in the mechanism of respiratory complex I,” Nature Communications, vol. 11, no. 1. Springer Nature, 2020.","mla":"Gutierrez-Fernandez, Javier, et al. “Key Role of Quinone in the Mechanism of Respiratory Complex I.” Nature Communications, vol. 11, no. 1, 4135, Springer Nature, 2020, doi:10.1038/s41467-020-17957-0.","ista":"Gutierrez-Fernandez J, Kaszuba K, Minhas GS, Baradaran R, Tambalo M, Gallagher DT, Sazanov LA. 2020. Key role of quinone in the mechanism of respiratory complex I. Nature Communications. 11(1), 4135.","chicago":"Gutierrez-Fernandez, Javier, Karol Kaszuba, Gurdeep S. Minhas, Rozbeh Baradaran, Margherita Tambalo, David T. Gallagher, and Leonid A Sazanov. “Key Role of Quinone in the Mechanism of Respiratory Complex I.” Nature Communications. Springer Nature, 2020. https://doi.org/10.1038/s41467-020-17957-0."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"last_name":"Gutierrez-Fernandez","full_name":"Gutierrez-Fernandez, Javier","first_name":"Javier","id":"3D9511BA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Kaszuba","full_name":"Kaszuba, Karol","first_name":"Karol","id":"3FDF9472-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Minhas, Gurdeep S.","last_name":"Minhas","first_name":"Gurdeep S."},{"last_name":"Baradaran","full_name":"Baradaran, Rozbeh","first_name":"Rozbeh"},{"last_name":"Tambalo","full_name":"Tambalo, Margherita","first_name":"Margherita","id":"4187dfe4-ec23-11ea-ae46-f08ab378313a"},{"first_name":"David T.","full_name":"Gallagher, David T.","last_name":"Gallagher"},{"last_name":"Sazanov","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","first_name":"Leonid A"}],"article_processing_charge":"No","external_id":{"pmid":["32811817"],"isi":["000607072900001"]},"title":"Key role of quinone in the mechanism of respiratory complex I","acknowledgement":"This work was funded by the Medical Research Council, UK and IST Austria. We thank the European Synchrotron Radiation Facility and the Diamond Light Source for provision of synchrotron radiation facilities. We are grateful to the staff of beamlines ID29, ID23-2 (ESRF, Grenoble, France) and I03 (Diamond Light Source, Didcot, UK) for assistance. Data processing was performed at the IST high-performance computing cluster.","quality_controlled":"1","publisher":"Springer Nature","oa":1,"isi":1,"has_accepted_license":"1","year":"2020","day":"18","publication":"Nature Communications","date_published":"2020-08-18T00:00:00Z","doi":"10.1038/s41467-020-17957-0","date_created":"2020-08-30T22:01:10Z","_id":"8318","article_type":"original","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","date_updated":"2023-08-22T09:03:00Z","ddc":["570"],"file_date_updated":"2020-08-31T13:40:00Z","department":[{"_id":"LeSa"}],"abstract":[{"text":"Complex I is the first and the largest enzyme of respiratory chains in bacteria and mitochondria. The mechanism which couples spatially separated transfer of electrons to proton translocation in complex I is not known. Here we report five crystal structures of T. thermophilus enzyme in complex with NADH or quinone-like compounds. We also determined cryo-EM structures of major and minor native states of the complex, differing in the position of the peripheral arm. Crystal structures show that binding of quinone-like compounds (but not of NADH) leads to a related global conformational change, accompanied by local re-arrangements propagating from the quinone site to the nearest proton channel. Normal mode and molecular dynamics analyses indicate that these are likely to represent the first steps in the proton translocation mechanism. Our results suggest that quinone binding and chemistry play a key role in the coupling mechanism of complex I.","lang":"eng"}],"pmid":1,"oa_version":"Published Version","scopus_import":"1","month":"08","intvolume":" 11","publication_identifier":{"eissn":["20411723"]},"publication_status":"published","file":[{"file_name":"2020_NatComm_Gutierrez-Fernandez.pdf","date_created":"2020-08-31T13:40:00Z","file_size":7527373,"date_updated":"2020-08-31T13:40:00Z","creator":"cziletti","success":1,"checksum":"52b96f41d7d0db9728064c08da00d030","file_id":"8326","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"language":[{"iso":"eng"}],"issue":"1","volume":11,"related_material":{"link":[{"url":"https://ist.ac.at/en/news/mystery-of-giant-proton-pump-solved/","relation":"press_release","description":"News on IST Homepage"}]},"license":"https://creativecommons.org/licenses/by/4.0/"},{"department":[{"_id":"LeSa"}],"file_date_updated":"2020-09-28T11:36:50Z","ddc":["570"],"date_updated":"2023-08-22T09:34:06Z","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","type":"journal_article","_id":"8579","volume":10,"issue":"9","language":[{"iso":"eng"}],"file":[{"date_created":"2020-09-28T11:36:50Z","file_name":"2020_Membranes_Andrei.pdf","date_updated":"2020-09-28T11:36:50Z","file_size":4612258,"creator":"dernst","checksum":"ceb43d7554e712dea6f36f9287271737","file_id":"8583","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file"}],"publication_status":"published","publication_identifier":{"eissn":["20770375"]},"intvolume":" 10","month":"09","scopus_import":"1","oa_version":"Published Version","abstract":[{"lang":"eng","text":"Copper (Cu) is an essential trace element for all living organisms and used as cofactor in key enzymes of important biological processes, such as aerobic respiration or superoxide dismutation. However, due to its toxicity, cells have developed elaborate mechanisms for Cu homeostasis, which balance Cu supply for cuproprotein biogenesis with the need to remove excess Cu. This review summarizes our current knowledge on bacterial Cu homeostasis with a focus on Gram-negative bacteria and describes the multiple strategies that bacteria use for uptake, storage and export of Cu. We furthermore describe general mechanistic principles that aid the bacterial response to toxic Cu concentrations and illustrate dedicated Cu relay systems that facilitate Cu delivery for cuproenzyme biogenesis. Progress in understanding how bacteria avoid Cu poisoning while maintaining a certain Cu quota for cell proliferation is of particular importance for microbial pathogens because Cu is utilized by the host immune system for attenuating pathogen survival in host cells."}],"title":"Cu homeostasis in bacteria: The ins and outs","external_id":{"isi":["000581446000001"]},"article_processing_charge":"No","author":[{"first_name":"Andreea","last_name":"Andrei","full_name":"Andrei, Andreea"},{"first_name":"Yavuz","last_name":"Öztürk","full_name":"Öztürk, Yavuz"},{"first_name":"Bahia","full_name":"Khalfaoui-Hassani, Bahia","last_name":"Khalfaoui-Hassani"},{"first_name":"Juna","full_name":"Rauch, Juna","last_name":"Rauch"},{"first_name":"Dorian","full_name":"Marckmann, Dorian","last_name":"Marckmann"},{"full_name":"Trasnea, Petru Iulian","last_name":"Trasnea","first_name":"Petru Iulian","id":"D560034C-10C4-11EA-ABF4-A4B43DDC885E"},{"last_name":"Daldal","full_name":"Daldal, Fevzi","first_name":"Fevzi"},{"first_name":"Hans-Georg","full_name":"Koch, Hans-Georg","last_name":"Koch"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"chicago":"Andrei, Andreea, Yavuz Öztürk, Bahia Khalfaoui-Hassani, Juna Rauch, Dorian Marckmann, Petru Iulian Trasnea, Fevzi Daldal, and Hans-Georg Koch. “Cu Homeostasis in Bacteria: The Ins and Outs.” Membranes. MDPI, 2020. https://doi.org/10.3390/membranes10090242.","ista":"Andrei A, Öztürk Y, Khalfaoui-Hassani B, Rauch J, Marckmann D, Trasnea PI, Daldal F, Koch H-G. 2020. Cu homeostasis in bacteria: The ins and outs. Membranes. 10(9), 242.","mla":"Andrei, Andreea, et al. “Cu Homeostasis in Bacteria: The Ins and Outs.” Membranes, vol. 10, no. 9, 242, MDPI, 2020, doi:10.3390/membranes10090242.","apa":"Andrei, A., Öztürk, Y., Khalfaoui-Hassani, B., Rauch, J., Marckmann, D., Trasnea, P. I., … Koch, H.-G. (2020). Cu homeostasis in bacteria: The ins and outs. Membranes. MDPI. https://doi.org/10.3390/membranes10090242","ama":"Andrei A, Öztürk Y, Khalfaoui-Hassani B, et al. Cu homeostasis in bacteria: The ins and outs. Membranes. 2020;10(9). doi:10.3390/membranes10090242","short":"A. Andrei, Y. Öztürk, B. Khalfaoui-Hassani, J. Rauch, D. Marckmann, P.I. Trasnea, F. Daldal, H.-G. Koch, Membranes 10 (2020).","ieee":"A. Andrei et al., “Cu homeostasis in bacteria: The ins and outs,” Membranes, vol. 10, no. 9. MDPI, 2020."},"article_number":"242","date_created":"2020-09-28T08:59:26Z","date_published":"2020-09-01T00:00:00Z","doi":"10.3390/membranes10090242","publication":"Membranes","day":"01","year":"2020","has_accepted_license":"1","isi":1,"oa":1,"quality_controlled":"1","publisher":"MDPI"},{"issue":"11","related_material":{"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/structure-of-atpase-solved/"}]},"volume":27,"language":[{"iso":"eng"}],"publication_identifier":{"issn":["15459993"],"eissn":["15459985"]},"publication_status":"published","month":"11","intvolume":" 27","scopus_import":"1","oa_version":"None","pmid":1,"abstract":[{"text":"The majority of adenosine triphosphate (ATP) powering cellular processes in eukaryotes is produced by the mitochondrial F1Fo ATP synthase. Here, we present the atomic models of the membrane Fo domain and the entire mammalian (ovine) F1Fo, determined by cryo-electron microscopy. Subunits in the membrane domain are arranged in the ‘proton translocation cluster’ attached to the c-ring and a more distant ‘hook apparatus’ holding subunit e. Unexpectedly, this subunit is anchored to a lipid ‘plug’ capping the c-ring. We present a detailed proton translocation pathway in mammalian Fo and key inter-monomer contacts in F1Fo multimers. Cryo-EM maps of F1Fo exposed to calcium reveal a retracted subunit e and a disassembled c-ring, suggesting permeability transition pore opening. We propose a model for the permeability transition pore opening, whereby subunit e pulls the lipid plug out of the c-ring. Our structure will allow the design of drugs for many emerging applications in medicine.","lang":"eng"}],"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"ScienComp"}],"department":[{"_id":"LeSa"}],"date_updated":"2023-08-22T09:33:09Z","status":"public","type":"journal_article","article_type":"original","_id":"8581","doi":"10.1038/s41594-020-0503-8","date_published":"2020-11-01T00:00:00Z","date_created":"2020-09-28T08:59:27Z","page":"1077-1085","day":"01","publication":"Nature Structural and Molecular Biology","isi":1,"year":"2020","publisher":"Springer Nature","quality_controlled":"1","acknowledgement":"We thank J. Novacek from CEITEC (Brno, Czech Republic) for assistance with collecting the FEI Krios dataset and iNEXT for providing access to CEITEC. We thank the IST Austria EM facility for access and assistance with collecting the FEI Glacios dataset. Data processing was performed at the IST high-performance computing cluster. This work has been supported by iNEXT EM HEDC (proposal 4506), funded by the Horizon 2020 Programme of the European Commission.","title":"Cryo-EM structure of the entire mammalian F-type ATP synthase","author":[{"id":"4D5303E6-F248-11E8-B48F-1D18A9856A87","first_name":"Gergely","last_name":"Pinke","full_name":"Pinke, Gergely"},{"full_name":"Zhou, Long","orcid":"0000-0002-1864-8951","last_name":"Zhou","id":"3E751364-F248-11E8-B48F-1D18A9856A87","first_name":"Long"},{"id":"338D39FE-F248-11E8-B48F-1D18A9856A87","first_name":"Leonid A","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","last_name":"Sazanov"}],"external_id":{"pmid":["32929284"],"isi":["000569299400004"]},"article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"apa":"Pinke, G., Zhou, L., & Sazanov, L. A. (2020). Cryo-EM structure of the entire mammalian F-type ATP synthase. Nature Structural and Molecular Biology. Springer Nature. https://doi.org/10.1038/s41594-020-0503-8","ama":"Pinke G, Zhou L, Sazanov LA. Cryo-EM structure of the entire mammalian F-type ATP synthase. Nature Structural and Molecular Biology. 2020;27(11):1077-1085. doi:10.1038/s41594-020-0503-8","ieee":"G. Pinke, L. Zhou, and L. A. Sazanov, “Cryo-EM structure of the entire mammalian F-type ATP synthase,” Nature Structural and Molecular Biology, vol. 27, no. 11. Springer Nature, pp. 1077–1085, 2020.","short":"G. Pinke, L. Zhou, L.A. Sazanov, Nature Structural and Molecular Biology 27 (2020) 1077–1085.","mla":"Pinke, Gergely, et al. “Cryo-EM Structure of the Entire Mammalian F-Type ATP Synthase.” Nature Structural and Molecular Biology, vol. 27, no. 11, Springer Nature, 2020, pp. 1077–85, doi:10.1038/s41594-020-0503-8.","ista":"Pinke G, Zhou L, Sazanov LA. 2020. Cryo-EM structure of the entire mammalian F-type ATP synthase. Nature Structural and Molecular Biology. 27(11), 1077–1085.","chicago":"Pinke, Gergely, Long Zhou, and Leonid A Sazanov. “Cryo-EM Structure of the Entire Mammalian F-Type ATP Synthase.” Nature Structural and Molecular Biology. Springer Nature, 2020. https://doi.org/10.1038/s41594-020-0503-8."}},{"project":[{"grant_number":"665385","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"article_number":"eabc4209","author":[{"full_name":"Kampjut, Domen","last_name":"Kampjut","id":"37233050-F248-11E8-B48F-1D18A9856A87","first_name":"Domen"},{"orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","last_name":"Sazanov","first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87"}],"external_id":{"pmid":["32972993"],"isi":["000583031800004"]},"article_processing_charge":"No","title":"The coupling mechanism of mammalian respiratory complex I","citation":{"ista":"Kampjut D, Sazanov LA. 2020. The coupling mechanism of mammalian respiratory complex I. Science. 370(6516), eabc4209.","chicago":"Kampjut, Domen, and Leonid A Sazanov. “The Coupling Mechanism of Mammalian Respiratory Complex I.” Science. American Association for the Advancement of Science, 2020. https://doi.org/10.1126/science.abc4209.","ama":"Kampjut D, Sazanov LA. The coupling mechanism of mammalian respiratory complex I. Science. 2020;370(6516). doi:10.1126/science.abc4209","apa":"Kampjut, D., & Sazanov, L. A. (2020). The coupling mechanism of mammalian respiratory complex I. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.abc4209","short":"D. Kampjut, L.A. Sazanov, Science 370 (2020).","ieee":"D. Kampjut and L. A. Sazanov, “The coupling mechanism of mammalian respiratory complex I,” Science, vol. 370, no. 6516. American Association for the Advancement of Science, 2020.","mla":"Kampjut, Domen, and Leonid A. Sazanov. “The Coupling Mechanism of Mammalian Respiratory Complex I.” Science, vol. 370, no. 6516, eabc4209, American Association for the Advancement of Science, 2020, doi:10.1126/science.abc4209."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","quality_controlled":"1","publisher":"American Association for the Advancement of Science","oa":1,"acknowledgement":"We thank J. Novacek (CEITEC Brno) and V.-V. Hodirnau (IST Austria) for their help with collecting cryo-EM datasets. We thank the IST Life Science and Electron Microscopy Facilities for providing equipment. This work has been supported by iNEXT,project number 653706, funded by the Horizon 2020 program of the European Union. This article reflects only the authors’view,and the European Commission is not responsible for any use that may be made of the information it contains. CIISB research infrastructure project LM2015043 funded by MEYS CR is gratefully acknowledged for the financial support of the measurements at the CF Cryo-electron Microscopy and Tomography CEITEC MU.This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant Agreement no. 665385","doi":"10.1126/science.abc4209","date_published":"2020-10-30T00:00:00Z","date_created":"2020-11-08T23:01:23Z","has_accepted_license":"1","isi":1,"year":"2020","day":"30","publication":"Science","type":"journal_article","article_type":"original","status":"public","_id":"8737","department":[{"_id":"LeSa"}],"file_date_updated":"2020-11-26T18:47:58Z","date_updated":"2023-08-22T12:35:38Z","ddc":["572"],"scopus_import":"1","month":"10","intvolume":" 370","abstract":[{"text":"Mitochondrial complex I couples NADH:ubiquinone oxidoreduction to proton pumping by an unknown mechanism. Here, we present cryo-electron microscopy structures of ovine complex I in five different conditions, including turnover, at resolutions up to 2.3 to 2.5 angstroms. Resolved water molecules allowed us to experimentally define the proton translocation pathways. Quinone binds at three positions along the quinone cavity, as does the inhibitor rotenone that also binds within subunit ND4. Dramatic conformational changes around the quinone cavity couple the redox reaction to proton translocation during open-to-closed state transitions of the enzyme. In the induced deactive state, the open conformation is arrested by the ND6 subunit. We propose a detailed molecular coupling mechanism of complex I, which is an unexpected combination of conformational changes and electrostatic interactions.","lang":"eng"}],"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"EM-Fac"}],"pmid":1,"oa_version":"Submitted Version","volume":370,"issue":"6516","ec_funded":1,"publication_identifier":{"eissn":["10959203"]},"publication_status":"published","file":[{"success":1,"checksum":"658ba90979ca9528a2efdfac8547047a","file_id":"8820","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"Full_manuscript_with_SI_opt_red.pdf","date_created":"2020-11-26T18:47:58Z","creator":"lsazanov","file_size":7618987,"date_updated":"2020-11-26T18:47:58Z"}],"language":[{"iso":"eng"}]},{"project":[{"_id":"26169496-B435-11E9-9278-68D0E5697425","grant_number":"24741","name":"Revealing the functional mechanism of Mrp antiporter, an ancestor of complex I"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ista":"Steiner J. 2020. Biochemical and structural investigation of the Mrp antiporter, an ancestor of complex I. Institute of Science and Technology Austria.","chicago":"Steiner, Julia. “Biochemical and Structural Investigation of the Mrp Antiporter, an Ancestor of Complex I.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8353.","ama":"Steiner J. Biochemical and structural investigation of the Mrp antiporter, an ancestor of complex I. 2020. doi:10.15479/AT:ISTA:8353","apa":"Steiner, J. (2020). Biochemical and structural investigation of the Mrp antiporter, an ancestor of complex I. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8353","ieee":"J. Steiner, “Biochemical and structural investigation of the Mrp antiporter, an ancestor of complex I,” Institute of Science and Technology Austria, 2020.","short":"J. Steiner, Biochemical and Structural Investigation of the Mrp Antiporter, an Ancestor of Complex I, Institute of Science and Technology Austria, 2020.","mla":"Steiner, Julia. Biochemical and Structural Investigation of the Mrp Antiporter, an Ancestor of Complex I. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8353."},"title":"Biochemical and structural investigation of the Mrp antiporter, an ancestor of complex I","article_processing_charge":"No","author":[{"first_name":"Julia","id":"3BB67EB0-F248-11E8-B48F-1D18A9856A87","last_name":"Steiner","full_name":"Steiner, Julia","orcid":"0000-0003-0493-3775"}],"acknowledgement":"I acknowledge the scientific service units of the IST Austria for providing resources by the Life Science Facility, the Electron Microscopy Facility and the high-performance computer cluster. Special thanks to the cryo-EM specialists Valentin Hodirnau and Daniel Johann Gütl for spending many hours with me in front of the microscope and for supporting me to collect the data presented here. I also want to thank Professor Masahiro Ito for providing plasmid DNA\r\nencoding Mrp from Anoxybacillus flavithermus WK1. I am a recipient of a DOC Fellowship of the Austrian Academy of Sciences.","oa":1,"publisher":"Institute of Science and Technology Austria","day":"09","year":"2020","has_accepted_license":"1","date_created":"2020-09-09T14:27:01Z","date_published":"2020-09-09T00:00:00Z","doi":"10.15479/AT:ISTA:8353","page":"191","_id":"8353","status":"public","type":"dissertation","ddc":["572"],"date_updated":"2023-09-07T13:14:09Z","supervisor":[{"first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","last_name":"Sazanov"}],"department":[{"_id":"LeSa"}],"file_date_updated":"2021-09-16T12:40:56Z","oa_version":"None","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"EM-Fac"},{"_id":"ScienComp"}],"abstract":[{"lang":"eng","text":"Mrp (Multi resistance and pH adaptation) are broadly distributed secondary active antiporters that catalyze the transport of monovalent ions such as sodium and potassium outside of the cell coupled to the inward translocation of protons. Mrp antiporters are unique in a way that they are composed of seven subunits (MrpABCDEFG) encoded in a single operon, whereas other antiporters catalyzing the same reaction are mostly encoded by a single gene. Mrp exchangers are crucial for intracellular pH homeostasis and Na+ efflux, essential mechanisms for H+ uptake under alkaline environments and for reduction of the intracellular concentration of toxic cations. Mrp displays no homology to any other monovalent Na+(K+)/H+ antiporters but Mrp subunits have primary sequence similarity to essential redox-driven proton pumps, such as respiratory complex I and membrane-bound hydrogenases. This similarity reinforces the hypothesis that these present day redox-driven proton pumps are descended from the Mrp antiporter. The Mrp structure serves as a model to understand the yet obscure coupling mechanism between ion or electron transfer and proton translocation in this large group of proteins. In the thesis, I am presenting the purification, biochemical analysis, cryo-EM analysis and molecular structure of the Mrp complex from Anoxybacillus flavithermus solved by cryo-EM at 3.0 Å resolution. Numerous conditions were screened to purify Mrp to high homogeneity and to obtain an appropriate distribution of single particles on cryo-EM grids covered with a continuous layer of ultrathin carbon. A preferred particle orientation problem was solved by performing a tilted data collection. The activity assays showed the specific pH-dependent\r\nprofile of secondary active antiporters. The molecular structure shows that Mrp is a dimer of seven-subunit protomers with 50 trans-membrane helices each. The dimer interface is built by many short and tilted transmembrane helices, probably causing a thinning of the bacterial membrane. The surface charge distribution shows an extraordinary asymmetry within each monomer, revealing presumable proton and sodium translocation pathways. The two largest\r\nand homologous Mrp subunits MrpA and MrpD probably translocate one proton each into the cell. The sodium ion is likely being translocated in the opposite direction within the small subunits along a ladder of charged and conserved residues. Based on the structure, we propose a mechanism were the antiport activity is accomplished via electrostatic interactions between the charged cations and key charged residues. The flexible key TM helices coordinate these\r\nelectrostatic interactions, while the membrane thinning between the monomers enables the translocation of sodium across the charged membrane. The entire family of redox-driven proton pumps is likely to perform their mechanism in a likewise manner."}],"month":"09","alternative_title":["ISTA Thesis"],"language":[{"iso":"eng"}],"file":[{"file_name":"Thesis_Julia_Steiner_pdfA.pdf","date_created":"2020-09-09T14:22:35Z","file_size":117547589,"date_updated":"2021-09-16T12:40:56Z","creator":"jsteiner","checksum":"2388d7e6e7a4d364c096fa89f305c3de","file_id":"8354","content_type":"application/pdf","relation":"main_file","access_level":"open_access"},{"checksum":"ba112f957b7145462d0ab79044873ee9","file_id":"8355","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","access_level":"closed","file_name":"Thesis_Julia_Steiner.docx","date_created":"2020-09-09T14:23:25Z","file_size":223328668,"date_updated":"2020-09-15T08:48:37Z","creator":"jsteiner"}],"degree_awarded":"PhD","publication_status":"published","publication_identifier":{"issn":["2663-337X"]},"related_material":{"record":[{"id":"8284","status":"public","relation":"part_of_dissertation"}]}},{"acknowledgement":"This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Electron Microscopy Facility (EMF), the Life Science Facility (LSF) and the IST high-performance computing cluster. We thank Dr Victor-Valentin Hodirnau and Daniel Johann Gütl from IST Austria for assistance with collecting cryo-EM data. We thank Prof. Masahiro Ito (Graduate School of Life Sciences, Toyo University, Japan) for a kind provision of plasmid DNA encoding Mrp from A. flavithermus WK1. JS is a recipient of a DOC Fellowship of the Austrian Academy of Sciences at the Institute of Science and Technology, Austria.","oa":1,"quality_controlled":"1","publisher":"eLife Sciences Publications","publication":"eLife","day":"31","year":"2020","isi":1,"has_accepted_license":"1","date_created":"2020-08-24T06:24:04Z","doi":"10.7554/eLife.59407","date_published":"2020-07-31T00:00:00Z","article_number":"e59407","project":[{"_id":"26169496-B435-11E9-9278-68D0E5697425","name":"Revealing the functional mechanism of Mrp antiporter, an ancestor of complex I","grant_number":"24741"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"chicago":"Steiner, Julia, and Leonid A Sazanov. “Structure and Mechanism of the Mrp Complex, an Ancient Cation/Proton Antiporter.” ELife. eLife Sciences Publications, 2020. https://doi.org/10.7554/eLife.59407.","ista":"Steiner J, Sazanov LA. 2020. Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter. eLife. 9, e59407.","mla":"Steiner, Julia, and Leonid A. Sazanov. “Structure and Mechanism of the Mrp Complex, an Ancient Cation/Proton Antiporter.” ELife, vol. 9, e59407, eLife Sciences Publications, 2020, doi:10.7554/eLife.59407.","apa":"Steiner, J., & Sazanov, L. A. (2020). Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.59407","ama":"Steiner J, Sazanov LA. Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter. eLife. 2020;9. doi:10.7554/eLife.59407","short":"J. Steiner, L.A. Sazanov, ELife 9 (2020).","ieee":"J. Steiner and L. A. Sazanov, “Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter,” eLife, vol. 9. eLife Sciences Publications, 2020."},"title":"Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter","external_id":{"pmid":["32735215"],"isi":["000562123600001"]},"article_processing_charge":"No","author":[{"last_name":"Steiner","orcid":"0000-0003-0493-3775","full_name":"Steiner, Julia","id":"3BB67EB0-F248-11E8-B48F-1D18A9856A87","first_name":"Julia"},{"full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989","last_name":"Sazanov","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","first_name":"Leonid A"}],"oa_version":"Published Version","pmid":1,"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"}],"abstract":[{"text":"Multiple resistance and pH adaptation (Mrp) antiporters are multi-subunit Na+ (or K+)/H+ exchangers representing an ancestor of many essential redox-driven proton pumps, such as respiratory complex I. The mechanism of coupling between ion or electron transfer and proton translocation in this large protein family is unknown. Here, we present the structure of the Mrp complex from Anoxybacillus flavithermus solved by cryo-EM at 3.0 Å resolution. It is a dimer of seven-subunit protomers with 50 trans-membrane helices each. Surface charge distribution within each monomer is remarkably asymmetric, revealing probable proton and sodium translocation pathways. On the basis of the structure we propose a mechanism where the coupling between sodium and proton translocation is facilitated by a series of electrostatic interactions between a cation and key charged residues. This mechanism is likely to be applicable to the entire family of redox proton pumps, where electron transfer to substrates replaces cation movements.","lang":"eng"}],"intvolume":" 9","month":"07","scopus_import":"1","language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","success":1,"file_id":"8289","checksum":"b3656d14d5ddbb9d26e3074eea2d0c15","file_size":7320493,"date_updated":"2020-08-24T13:31:53Z","creator":"cziletti","file_name":"2020_eLife_Steiner.pdf","date_created":"2020-08-24T13:31:53Z"}],"publication_status":"published","publication_identifier":{"eissn":["2050084X"]},"related_material":{"link":[{"description":"News on IST Homepage","url":"https://ist.ac.at/en/news/mystery-of-giant-proton-pump-solved/","relation":"press_release"}],"record":[{"status":"public","id":"8353","relation":"dissertation_contains"}]},"volume":9,"_id":"8284","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","type":"journal_article","ddc":["570"],"date_updated":"2023-09-07T13:14:08Z","department":[{"_id":"LeSa"}],"file_date_updated":"2020-08-24T13:31:53Z"},{"department":[{"_id":"LeSa"}],"file_date_updated":"2021-09-11T22:30:04Z","ddc":["572"],"supervisor":[{"last_name":"Sazanov","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2023-09-07T13:26:17Z","status":"public","type":"dissertation","_id":"8340","related_material":{"record":[{"status":"public","id":"6848","relation":"part_of_dissertation"}]},"ec_funded":1,"file":[{"file_id":"8345","checksum":"dd270baf82121eb4472ad19d77bf227c","access_level":"closed","relation":"source_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","embargo_to":"open_access","date_created":"2020-09-08T13:32:06Z","file_name":"ThesisFull20200908.docx","creator":"dkampjut","date_updated":"2021-09-11T22:30:04Z","file_size":166146359},{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"82fce6f95ffa47ecc4ebca67ea2cc38c","file_id":"8393","embargo":"2021-09-10","date_updated":"2021-09-11T22:30:04Z","file_size":13873769,"creator":"dernst","date_created":"2020-09-14T15:02:20Z","file_name":"2020_Thesis_Kampjut.pdf"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-008-4"]},"publication_status":"published","degree_awarded":"PhD","month":"09","alternative_title":["ISTA Thesis"],"oa_version":"None","abstract":[{"text":"Mitochondria are sites of oxidative phosphorylation in eukaryotic cells. Oxidative phosphorylation operates by a chemiosmotic mechanism made possible by redox-driven proton pumping machines which establish a proton motive force across the inner mitochondrial membrane. This electrochemical proton gradient is used to drive ATP synthesis, which powers the majority of cellular processes such as protein synthesis, locomotion and signalling. In this thesis I investigate the structures and molecular mechanisms of two inner mitochondrial proton pumping enzymes, respiratory complex I and transhydrogenase. I present the first high-resolution structure of the full transhydrogenase from any species, and a significantly improved structure of complex I. Improving the resolution from 3.3 Å available previously to up to 2.3 Å in this thesis allowed us to model bound water molecules, crucial in the proton pumping mechanism. For both enzymes, up to five cryo-EM datasets with different substrates and inhibitors bound were solved to delineate the catalytic cycle and understand the proton pumping mechanism. In transhydrogenase, the proton channel is gated by reversible detachment of the NADP(H)-binding domain which opens the proton channel to the opposite sites of the membrane. In complex I, the proton channels are gated by reversible protonation of key glutamate and lysine residues and breaking of the water wire connecting the proton pumps with the quinone reduction site. The tight coupling between the redox and the proton pumping reactions in transhydrogenase is achieved by controlling the NADP(H) exchange which can only happen when the NADP(H)-binding domain interacts with the membrane domain. In complex I, coupling is achieved by cycling of the whole complex between the closed state, in which quinone can get reduced, and the open state, in which NADH can induce quinol ejection from the binding pocket. On the basis of these results I propose detailed mechanisms for catalytic cycles of transhydrogenase and complex I that are consistent with a large amount of previous work. In both enzymes, conformational and electrostatic mechanisms contribute to the overall catalytic process. Results presented here could be used for better understanding of the human pathologies arising from deficiencies of complex I or transhydrogenase and could be used to develop novel therapies.","lang":"eng"}],"acknowledged_ssus":[{"_id":"EM-Fac"}],"title":"Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes","author":[{"first_name":"Domen","id":"37233050-F248-11E8-B48F-1D18A9856A87","full_name":"Kampjut, Domen","last_name":"Kampjut"}],"article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ista":"Kampjut D. 2020. Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes. Institute of Science and Technology Austria.","chicago":"Kampjut, Domen. “Molecular Mechanisms of Mitochondrial Redox-Coupled Proton Pumping Enzymes.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8340.","ama":"Kampjut D. Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes. 2020. doi:10.15479/AT:ISTA:8340","apa":"Kampjut, D. (2020). Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8340","ieee":"D. Kampjut, “Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes,” Institute of Science and Technology Austria, 2020.","short":"D. Kampjut, Molecular Mechanisms of Mitochondrial Redox-Coupled Proton Pumping Enzymes, Institute of Science and Technology Austria, 2020.","mla":"Kampjut, Domen. Molecular Mechanisms of Mitochondrial Redox-Coupled Proton Pumping Enzymes. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8340."},"project":[{"grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"}],"date_published":"2020-09-09T00:00:00Z","doi":"10.15479/AT:ISTA:8340","date_created":"2020-09-07T18:42:23Z","page":"242","day":"09","has_accepted_license":"1","year":"2020","publisher":"Institute of Science and Technology Austria","oa":1,"acknowledgement":"I acknowledge the support of IST facilities, especially the Electron Miscroscopy facility for providing training and resources. Special thanks also go to cryo-EM specialists who helped me to collect the data present here: Dr Valentin Hodirnau (IST Austria), Dr Tom Heuser (IMBA, Vienna), Dr Rebecca Thompson (Uni. of Leeds) and Dr Jirka Nováček (CEITEC). This work has been supported by iNEXT, project number 653706, funded by the Horizon 2020 programme of the European Union. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 665385."},{"department":[{"_id":"LeSa"}],"file_date_updated":"2020-07-14T12:47:28Z","date_updated":"2023-08-25T10:14:26Z","ddc":["570"],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","status":"public","_id":"6352","publication_status":"published","publication_identifier":{"issn":["03014851"],"eissn":["15734978"]},"language":[{"iso":"eng"}],"file":[{"file_size":1948014,"date_updated":"2020-07-14T12:47:28Z","creator":"dernst","file_name":"2019_MolecularBioReport_Temnov.pdf","date_created":"2019-04-30T09:52:36Z","content_type":"application/pdf","relation":"main_file","access_level":"open_access","checksum":"45bf040bbce1cea274f6013fa18ba21b","file_id":"6362"}],"scopus_import":"1","month":"04","abstract":[{"text":"Chronic overuse of common pharmaceuticals, e.g. acetaminophen (paracetamol), often leads to the development of acute liver failure (ALF). This study aimed to elucidate the effect of cultured mesenchymal stem cells (MSCs) proteome on the onset of liver damage and regeneration dynamics in animals with ALF induced by acetaminophen, to test the liver protective efficacy of MSCs proteome depending on the oxygen tension in cell culture, and to blueprint protein components responsible for the effect. Protein compositions prepared from MSCs cultured in mild hypoxic (5% and 10% O2) and normal (21% O2) conditions were used to treat ALF induced in mice by injection of acetaminophen. To test the effect of reduced oxygen tension in cell culture on resulting MSCs proteome content we applied a combination of high performance liquid chromatography and mass-spectrometry (LC–MS/MS) for the identification of proteins in lysates of MSCs cultured at different O2 levels. The treatment of acetaminophen-administered animals with proteins released from cultured MSCs resulted in the inhibition of inflammatory reactions in damaged liver; the area of hepatocyte necrosis being reduced in the first 24 h. Compositions obtained from MSCs cultured at lower O2 level were shown to be more potent than a composition prepared from normoxic cells. A comparative characterization of protein pattern and identification of individual components done by a cytokine assay and proteomics analysis of protein compositions revealed that even moderate hypoxia produces discrete changes in the expression of various subsets of proteins responsible for intracellular respiration and cell signaling. The application of proteins prepared from MSCs grown in vitro at reduced oxygen tension significantly accelerates healing process in damaged liver tissue. The proteomics data obtained for different preparations offer new information about the potential candidates in the MSCs protein repertoire sensitive to oxygen tension in culture medium, which can be involved in the generalized mechanisms the cells use to respond to acute liver failure.","lang":"eng"}],"oa_version":"Published Version","external_id":{"isi":["000470332600049"]},"article_processing_charge":"Yes (via OA deal)","author":[{"first_name":"Andrey Alexandrovich","full_name":"Temnov, Andrey Alexandrovich","last_name":"Temnov"},{"last_name":"Rogov","full_name":"Rogov, Konstantin Arkadevich","first_name":"Konstantin Arkadevich"},{"last_name":"Sklifas","full_name":"Sklifas, Alla Nikolaevna","first_name":"Alla Nikolaevna"},{"full_name":"Klychnikova, Elena Valerievna","last_name":"Klychnikova","first_name":"Elena Valerievna"},{"full_name":"Hartl, Markus","last_name":"Hartl","first_name":"Markus"},{"full_name":"Djinovic-Carugo, Kristina","last_name":"Djinovic-Carugo","first_name":"Kristina"},{"last_name":"Charnagalov","full_name":"Charnagalov, Alexej","id":"49F06DBA-F248-11E8-B48F-1D18A9856A87","first_name":"Alexej"}],"title":"Protective properties of the cultured stem cell proteome studied in an animal model of acetaminophen-induced acute liver failure","citation":{"chicago":"Temnov, Andrey Alexandrovich, Konstantin Arkadevich Rogov, Alla Nikolaevna Sklifas, Elena Valerievna Klychnikova, Markus Hartl, Kristina Djinovic-Carugo, and Alexej Charnagalov. “Protective Properties of the Cultured Stem Cell Proteome Studied in an Animal Model of Acetaminophen-Induced Acute Liver Failure.” Molecular Biology Reports. Springer, 2019. https://doi.org/10.1007/s11033-019-04765-z.","ista":"Temnov AA, Rogov KA, Sklifas AN, Klychnikova EV, Hartl M, Djinovic-Carugo K, Charnagalov A. 2019. Protective properties of the cultured stem cell proteome studied in an animal model of acetaminophen-induced acute liver failure. Molecular Biology Reports.","mla":"Temnov, Andrey Alexandrovich, et al. “Protective Properties of the Cultured Stem Cell Proteome Studied in an Animal Model of Acetaminophen-Induced Acute Liver Failure.” Molecular Biology Reports, Springer, 2019, doi:10.1007/s11033-019-04765-z.","ama":"Temnov AA, Rogov KA, Sklifas AN, et al. Protective properties of the cultured stem cell proteome studied in an animal model of acetaminophen-induced acute liver failure. Molecular Biology Reports. 2019. doi:10.1007/s11033-019-04765-z","apa":"Temnov, A. A., Rogov, K. A., Sklifas, A. N., Klychnikova, E. V., Hartl, M., Djinovic-Carugo, K., & Charnagalov, A. (2019). Protective properties of the cultured stem cell proteome studied in an animal model of acetaminophen-induced acute liver failure. Molecular Biology Reports. Springer. https://doi.org/10.1007/s11033-019-04765-z","ieee":"A. A. Temnov et al., “Protective properties of the cultured stem cell proteome studied in an animal model of acetaminophen-induced acute liver failure,” Molecular Biology Reports. Springer, 2019.","short":"A.A. Temnov, K.A. Rogov, A.N. Sklifas, E.V. Klychnikova, M. Hartl, K. Djinovic-Carugo, A. Charnagalov, Molecular Biology Reports (2019)."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_created":"2019-04-28T21:59:14Z","date_published":"2019-04-12T00:00:00Z","doi":"10.1007/s11033-019-04765-z","year":"2019","isi":1,"has_accepted_license":"1","publication":"Molecular Biology Reports","day":"12","oa":1,"quality_controlled":"1","publisher":"Springer","acknowledgement":"The studies were supported by the Austrian Federal Ministry of Economy, Family and Youth through the initiative “Laura Bassi Centres of Expertise” funding the Center of Optimized Structural Stud-ies, grant No. 253275"},{"department":[{"_id":"LeSa"}],"date_updated":"2023-08-29T07:52:02Z","status":"public","type":"journal_article","_id":"6859","related_material":{"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/structure-of-protein-nano-turbine-revealed/","description":"News on IST Website"}]},"volume":365,"issue":"6455","language":[{"iso":"eng"}],"publication_status":"published","publication_identifier":{"eissn":["1095-9203"],"issn":["0036-8075"]},"intvolume":" 365","month":"08","scopus_import":"1","oa_version":"None","pmid":1,"abstract":[{"lang":"eng","text":"V (vacuolar)/A (archaeal)-type adenosine triphosphatases (ATPases), found in archaeaand eubacteria, couple ATP hydrolysis or synthesis to proton translocation across theplasma membrane using the rotary-catalysis mechanism. They belong to the V-typeATPase family, which differs from the mitochondrial/chloroplast F-type ATP synthasesin overall architecture. We solved cryo–electron microscopy structures of the intactThermus thermophilusV/A-ATPase, reconstituted into lipid nanodiscs, in three rotationalstates and two substates. These structures indicate substantial flexibility betweenV1and Voin a working enzyme, which results from mechanical competition between centralshaft rotation and resistance from the peripheral stalks. We also describedetails of adenosine diphosphate inhibition release, V1-Votorque transmission, andproton translocation, which are relevant for the entire V-type ATPase family."}],"acknowledged_ssus":[{"_id":"ScienComp"}],"title":"Structure and conformational plasticity of the intact Thermus thermophilus V/A-type ATPase","article_processing_charge":"No","external_id":{"isi":["000482464000043"],"pmid":["31439765"]},"author":[{"id":"3E751364-F248-11E8-B48F-1D18A9856A87","first_name":"Long","last_name":"Zhou","full_name":"Zhou, Long","orcid":"0000-0002-1864-8951"},{"id":"338D39FE-F248-11E8-B48F-1D18A9856A87","first_name":"Leonid A","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","last_name":"Sazanov"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ista":"Zhou L, Sazanov LA. 2019. Structure and conformational plasticity of the intact Thermus thermophilus V/A-type ATPase. Science. 365(6455), eaaw9144.","chicago":"Zhou, Long, and Leonid A Sazanov. “Structure and Conformational Plasticity of the Intact Thermus Thermophilus V/A-Type ATPase.” Science. AAAS, 2019. https://doi.org/10.1126/science.aaw9144.","ama":"Zhou L, Sazanov LA. Structure and conformational plasticity of the intact Thermus thermophilus V/A-type ATPase. Science. 2019;365(6455). doi:10.1126/science.aaw9144","apa":"Zhou, L., & Sazanov, L. A. (2019). Structure and conformational plasticity of the intact Thermus thermophilus V/A-type ATPase. Science. AAAS. https://doi.org/10.1126/science.aaw9144","short":"L. Zhou, L.A. Sazanov, Science 365 (2019).","ieee":"L. Zhou and L. A. Sazanov, “Structure and conformational plasticity of the intact Thermus thermophilus V/A-type ATPase,” Science, vol. 365, no. 6455. AAAS, 2019.","mla":"Zhou, Long, and Leonid A. Sazanov. “Structure and Conformational Plasticity of the Intact Thermus Thermophilus V/A-Type ATPase.” Science, vol. 365, no. 6455, eaaw9144, AAAS, 2019, doi:10.1126/science.aaw9144."},"article_number":"eaaw9144","date_created":"2019-09-07T19:04:45Z","doi":"10.1126/science.aaw9144","date_published":"2019-08-23T00:00:00Z","publication":"Science","day":"23","year":"2019","isi":1,"publisher":"AAAS","quality_controlled":"1"},{"article_number":"eaaw6490","author":[{"full_name":"Qi, Chao","last_name":"Qi","first_name":"Chao"},{"full_name":"Minin, Giulio Di","last_name":"Minin","first_name":"Giulio Di"},{"last_name":"Vercellino","full_name":"Vercellino, Irene","orcid":"0000-0001-5618-3449","first_name":"Irene","id":"3ED6AF16-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Anton","full_name":"Wutz, Anton","last_name":"Wutz"},{"full_name":"Korkhov, Volodymyr M.","last_name":"Korkhov","first_name":"Volodymyr M."}],"external_id":{"isi":["000491128800062"]},"article_processing_charge":"No","title":"Structural basis of sterol recognition by human hedgehog receptor PTCH1","citation":{"ista":"Qi C, Minin GD, Vercellino I, Wutz A, Korkhov VM. 2019. Structural basis of sterol recognition by human hedgehog receptor PTCH1. Science Advances. 5(9), eaaw6490.","chicago":"Qi, Chao, Giulio Di Minin, Irene Vercellino, Anton Wutz, and Volodymyr M. Korkhov. “Structural Basis of Sterol Recognition by Human Hedgehog Receptor PTCH1.” Science Advances. American Association for the Advancement of Science, 2019. https://doi.org/10.1126/sciadv.aaw6490.","ieee":"C. Qi, G. D. Minin, I. Vercellino, A. Wutz, and V. M. Korkhov, “Structural basis of sterol recognition by human hedgehog receptor PTCH1,” Science Advances, vol. 5, no. 9. American Association for the Advancement of Science, 2019.","short":"C. Qi, G.D. Minin, I. Vercellino, A. Wutz, V.M. Korkhov, Science Advances 5 (2019).","apa":"Qi, C., Minin, G. D., Vercellino, I., Wutz, A., & Korkhov, V. M. (2019). Structural basis of sterol recognition by human hedgehog receptor PTCH1. Science Advances. American Association for the Advancement of Science. https://doi.org/10.1126/sciadv.aaw6490","ama":"Qi C, Minin GD, Vercellino I, Wutz A, Korkhov VM. Structural basis of sterol recognition by human hedgehog receptor PTCH1. Science Advances. 2019;5(9). doi:10.1126/sciadv.aaw6490","mla":"Qi, Chao, et al. “Structural Basis of Sterol Recognition by Human Hedgehog Receptor PTCH1.” Science Advances, vol. 5, no. 9, eaaw6490, American Association for the Advancement of Science, 2019, doi:10.1126/sciadv.aaw6490."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","quality_controlled":"1","publisher":"American Association for the Advancement of Science","oa":1,"doi":"10.1126/sciadv.aaw6490","date_published":"2019-09-18T00:00:00Z","date_created":"2019-09-29T22:00:45Z","has_accepted_license":"1","isi":1,"year":"2019","day":"18","publication":"Science Advances","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","short":"CC BY-NC (4.0)"},"status":"public","_id":"6919","department":[{"_id":"LeSa"}],"file_date_updated":"2020-07-14T12:47:44Z","date_updated":"2023-08-30T06:55:31Z","ddc":["570"],"scopus_import":"1","month":"09","intvolume":" 5","oa_version":"Published Version","volume":5,"issue":"9","license":"https://creativecommons.org/licenses/by-nc/4.0/","publication_identifier":{"eissn":["23752548"]},"publication_status":"published","file":[{"date_updated":"2020-07-14T12:47:44Z","file_size":1236101,"creator":"kschuh","date_created":"2019-10-02T11:13:54Z","file_name":"2019_AAAS_Qi.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"b2256c9117655bc15f621ba0babf219f","file_id":"6928"}],"language":[{"iso":"eng"}]},{"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"mla":"Letts, James A., et al. “Structures of Respiratory Supercomplex I+III2 Reveal Functional and Conformational Crosstalk.” Molecular Cell, vol. 75, no. 6, Cell Press, 2019, p. 1131–1146.e6, doi:10.1016/j.molcel.2019.07.022.","ama":"Letts JA, Fiedorczuk K, Degliesposti G, Skehel M, Sazanov LA. Structures of respiratory supercomplex I+III2 reveal functional and conformational crosstalk. Molecular Cell. 2019;75(6):1131-1146.e6. doi:10.1016/j.molcel.2019.07.022","apa":"Letts, J. A., Fiedorczuk, K., Degliesposti, G., Skehel, M., & Sazanov, L. A. (2019). Structures of respiratory supercomplex I+III2 reveal functional and conformational crosstalk. Molecular Cell. Cell Press. https://doi.org/10.1016/j.molcel.2019.07.022","ieee":"J. A. Letts, K. Fiedorczuk, G. Degliesposti, M. Skehel, and L. A. Sazanov, “Structures of respiratory supercomplex I+III2 reveal functional and conformational crosstalk,” Molecular Cell, vol. 75, no. 6. Cell Press, p. 1131–1146.e6, 2019.","short":"J.A. Letts, K. Fiedorczuk, G. Degliesposti, M. Skehel, L.A. Sazanov, Molecular Cell 75 (2019) 1131–1146.e6.","chicago":"Letts, James A, Karol Fiedorczuk, Gianluca Degliesposti, Mark Skehel, and Leonid A Sazanov. “Structures of Respiratory Supercomplex I+III2 Reveal Functional and Conformational Crosstalk.” Molecular Cell. Cell Press, 2019. https://doi.org/10.1016/j.molcel.2019.07.022.","ista":"Letts JA, Fiedorczuk K, Degliesposti G, Skehel M, Sazanov LA. 2019. Structures of respiratory supercomplex I+III2 reveal functional and conformational crosstalk. Molecular Cell. 75(6), 1131–1146.e6."},"title":"Structures of respiratory supercomplex I+III2 reveal functional and conformational crosstalk","article_processing_charge":"No","external_id":{"isi":["000486614200006"],"pmid":["31492636"]},"author":[{"id":"322DA418-F248-11E8-B48F-1D18A9856A87","first_name":"James A","last_name":"Letts","full_name":"Letts, James A","orcid":"0000-0002-9864-3586"},{"last_name":"Fiedorczuk","full_name":"Fiedorczuk, Karol","first_name":"Karol","id":"5BFF67CE-02D1-11E9-B11A-A5A4D7DFFFD0"},{"first_name":"Gianluca","last_name":"Degliesposti","full_name":"Degliesposti, Gianluca"},{"last_name":"Skehel","full_name":"Skehel, Mark","first_name":"Mark"},{"id":"338D39FE-F248-11E8-B48F-1D18A9856A87","first_name":"Leonid A","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","last_name":"Sazanov"}],"project":[{"name":"Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes","grant_number":"701309","_id":"2590DB08-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"publication":"Molecular Cell","day":"19","year":"2019","isi":1,"has_accepted_license":"1","date_created":"2020-01-29T16:02:33Z","doi":"10.1016/j.molcel.2019.07.022","date_published":"2019-09-19T00:00:00Z","page":"1131-1146.e6","oa":1,"quality_controlled":"1","publisher":"Cell Press","ddc":["570"],"date_updated":"2023-09-07T14:53:06Z","file_date_updated":"2020-07-14T12:47:57Z","department":[{"_id":"LeSa"}],"_id":"7395","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","type":"journal_article","language":[{"iso":"eng"}],"file":[{"date_created":"2020-02-04T10:37:28Z","file_name":"2019_MolecularCell_Letts.pdf","date_updated":"2020-07-14T12:47:57Z","file_size":9654895,"creator":"dernst","file_id":"7447","checksum":"5202f53a237d6650ece038fbf13bdcea","content_type":"application/pdf","access_level":"open_access","relation":"main_file"}],"publication_status":"published","publication_identifier":{"issn":["1097-2765"]},"ec_funded":1,"volume":75,"issue":"6","oa_version":"Published Version","pmid":1,"abstract":[{"text":"The mitochondrial electron transport chain complexes are organized into supercomplexes (SCs) of defined stoichiometry, which have been proposed to regulate electron flux via substrate channeling. We demonstrate that CoQ trapping in the isolated SC I+III2 limits complex (C)I turnover, arguing against channeling. The SC structure, resolved at up to 3.8 Å in four distinct states, suggests that CoQ oxidation may be rate limiting because of unequal access of CoQ to the active sites of CIII2. CI shows a transition between “closed” and “open” conformations, accompanied by the striking rotation of a key transmembrane helix. Furthermore, the state of CI affects the conformational flexibility within CIII2, demonstrating crosstalk between the enzymes. CoQ was identified at only three of the four binding sites in CIII2, suggesting that interaction with CI disrupts CIII2 symmetry in a functionally relevant manner. Together, these observations indicate a more nuanced functional role for the SCs.","lang":"eng"}],"intvolume":" 75","month":"09","scopus_import":"1"},{"date_created":"2019-09-04T06:21:41Z","date_published":"2019-09-12T00:00:00Z","doi":"10.1038/s41586-019-1519-2","page":"291–295","publication":"Nature","day":"12","year":"2019","has_accepted_license":"1","isi":1,"oa":1,"publisher":"Springer Nature","quality_controlled":"1","acknowledgement":" We thank R. Thompson, G. Effantin and V.-V. Hodirnau for their assistance with collecting NADP+, NADPH and apo datasets, respectively. Data processing was performed at the IST high-performance computing cluster.\r\nThis project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement no. 665385.","title":"Structure and mechanism of mitochondrial proton-translocating transhydrogenase","article_processing_charge":"No","external_id":{"pmid":["31462775"],"isi":["000485415400061"]},"author":[{"first_name":"Domen","id":"37233050-F248-11E8-B48F-1D18A9856A87","full_name":"Kampjut, Domen","last_name":"Kampjut"},{"first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","last_name":"Sazanov","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"chicago":"Kampjut, Domen, and Leonid A Sazanov. “Structure and Mechanism of Mitochondrial Proton-Translocating Transhydrogenase.” Nature. Springer Nature, 2019. https://doi.org/10.1038/s41586-019-1519-2.","ista":"Kampjut D, Sazanov LA. 2019. Structure and mechanism of mitochondrial proton-translocating transhydrogenase. Nature. 573(7773), 291–295.","mla":"Kampjut, Domen, and Leonid A. Sazanov. “Structure and Mechanism of Mitochondrial Proton-Translocating Transhydrogenase.” Nature, vol. 573, no. 7773, Springer Nature, 2019, pp. 291–295, doi:10.1038/s41586-019-1519-2.","ieee":"D. Kampjut and L. A. Sazanov, “Structure and mechanism of mitochondrial proton-translocating transhydrogenase,” Nature, vol. 573, no. 7773. Springer Nature, pp. 291–295, 2019.","short":"D. Kampjut, L.A. Sazanov, Nature 573 (2019) 291–295.","apa":"Kampjut, D., & Sazanov, L. A. (2019). Structure and mechanism of mitochondrial proton-translocating transhydrogenase. Nature. Springer Nature. https://doi.org/10.1038/s41586-019-1519-2","ama":"Kampjut D, Sazanov LA. Structure and mechanism of mitochondrial proton-translocating transhydrogenase. Nature. 2019;573(7773):291–295. doi:10.1038/s41586-019-1519-2"},"project":[{"name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"ec_funded":1,"related_material":{"record":[{"id":"8340","status":"public","relation":"dissertation_contains"}],"link":[{"description":"News on IST Website","relation":"press_release","url":"https://ist.ac.at/en/news/high-end-microscopy-reveals-structure-and-function-of-crucial-metabolic-enzyme/"}]},"volume":573,"issue":"7773","language":[{"iso":"eng"}],"file":[{"file_name":"Manuscript_final_acc_withFigs_SI_opt_red.pdf","date_created":"2020-11-26T16:33:44Z","creator":"lsazanov","file_size":3066206,"date_updated":"2020-11-26T16:33:44Z","success":1,"checksum":"52728cda5210a3e9b74cc204e8aed3d5","file_id":"8821","relation":"main_file","access_level":"open_access","content_type":"application/pdf"}],"publication_status":"published","publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"intvolume":" 573","month":"09","scopus_import":"1","pmid":1,"oa_version":"Submitted Version","abstract":[{"text":"Proton-translocating transhydrogenase (also known as nicotinamide nucleotide transhydrogenase (NNT)) is found in the plasma membranes of bacteria and the inner mitochondrial membranes of eukaryotes. NNT catalyses the transfer of a hydride between NADH and NADP+, coupled to the translocation of one proton across the membrane. Its main physiological function is the generation of NADPH, which is a substrate in anabolic reactions and a regulator of oxidative status; however, NNT may also fine-tune the Krebs cycle1,2. NNT deficiency causes familial glucocorticoid deficiency in humans and metabolic abnormalities in mice, similar to those observed in type II diabetes3,4. The catalytic mechanism of NNT has been proposed to involve a rotation of around 180° of the entire NADP(H)-binding domain that alternately participates in hydride transfer and proton-channel gating. However, owing to the lack of high-resolution structures of intact NNT, the details of this process remain unclear5,6. Here we present the cryo-electron microscopy structure of intact mammalian NNT in different conformational states. We show how the NADP(H)-binding domain opens the proton channel to the opposite sides of the membrane, and we provide structures of these two states. We also describe the catalytically important interfaces and linkers between the membrane and the soluble domains and their roles in nucleotide exchange. These structures enable us to propose a revised mechanism for a coupling process in NNT that is consistent with a large body of previous biochemical work. Our results are relevant to the development of currently unavailable NNT inhibitors, which may have therapeutic potential in ischaemia reperfusion injury, metabolic syndrome and some cancers7,8,9.","lang":"eng"}],"acknowledged_ssus":[{"_id":"ScienComp"}],"file_date_updated":"2020-11-26T16:33:44Z","department":[{"_id":"LeSa"}],"ddc":["572"],"date_updated":"2024-03-27T23:30:14Z","status":"public","article_type":"letter_note","type":"journal_article","_id":"6848"},{"abstract":[{"text":"Complex I has an essential role in ATP production by coupling electron transfer from NADH to quinone with translocation of protons across the inner mitochondrial membrane. Isolated complex I deficiency is a frequent cause of mitochondrial inherited diseases. Complex I has also been implicated in cancer, ageing, and neurodegenerative conditions. Until recently, the understanding of complex I deficiency on the molecular level was limited due to the lack of high-resolution structures of the enzyme. However, due to developments in single particle cryo-electron microscopy (cryo-EM), recent studies have reported nearly atomic resolution maps and models of mitochondrial complex I. These structures significantly add to our understanding of complex I mechanism and assembly. The disease-causing mutations are discussed here in their structural context.","lang":"eng"}],"oa_version":"Submitted Version","scopus_import":"1","intvolume":" 28","month":"07","publication_status":"published","language":[{"iso":"eng"}],"file":[{"date_created":"2019-11-07T12:55:20Z","file_name":"SasanovFinalMS+EdComments_LS_allacc_withFigs.pdf","creator":"lsazanov","date_updated":"2020-07-14T12:45:00Z","file_size":2185385,"file_id":"6994","checksum":"ef6d2b4e1fd63948539639242610bfa6","access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","volume":28,"issue":"10","_id":"152","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"article_type":"original","type":"journal_article","status":"public","date_updated":"2023-09-13T08:51:56Z","ddc":["572"],"file_date_updated":"2020-07-14T12:45:00Z","department":[{"_id":"LeSa"}],"oa":1,"publisher":"Elsevier","quality_controlled":"1","year":"2018","isi":1,"has_accepted_license":"1","publication":"Trends in Cell Biology","day":"26","page":"835 - 867","date_created":"2018-12-11T11:44:54Z","date_published":"2018-07-26T00:00:00Z","doi":"10.1016/j.tcb.2018.06.006","citation":{"short":"K. Fiedorczuk, L.A. Sazanov, Trends in Cell Biology 28 (2018) 835–867.","ieee":"K. Fiedorczuk and L. A. Sazanov, “Mammalian mitochondrial complex I structure and disease causing mutations,” Trends in Cell Biology, vol. 28, no. 10. Elsevier, pp. 835–867, 2018.","ama":"Fiedorczuk K, Sazanov LA. Mammalian mitochondrial complex I structure and disease causing mutations. Trends in Cell Biology. 2018;28(10):835-867. doi:10.1016/j.tcb.2018.06.006","apa":"Fiedorczuk, K., & Sazanov, L. A. (2018). Mammalian mitochondrial complex I structure and disease causing mutations. Trends in Cell Biology. Elsevier. https://doi.org/10.1016/j.tcb.2018.06.006","mla":"Fiedorczuk, Karol, and Leonid A. Sazanov. “Mammalian Mitochondrial Complex I Structure and Disease Causing Mutations.” Trends in Cell Biology, vol. 28, no. 10, Elsevier, 2018, pp. 835–67, doi:10.1016/j.tcb.2018.06.006.","ista":"Fiedorczuk K, Sazanov LA. 2018. Mammalian mitochondrial complex I structure and disease causing mutations. Trends in Cell Biology. 28(10), 835–867.","chicago":"Fiedorczuk, Karol, and Leonid A Sazanov. “Mammalian Mitochondrial Complex I Structure and Disease Causing Mutations.” Trends in Cell Biology. Elsevier, 2018. https://doi.org/10.1016/j.tcb.2018.06.006."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","external_id":{"isi":["000445118200007"]},"article_processing_charge":"No","author":[{"first_name":"Karol","id":"5BFF67CE-02D1-11E9-B11A-A5A4D7DFFFD0","last_name":"Fiedorczuk","full_name":"Fiedorczuk, Karol"},{"full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989","last_name":"Sazanov","first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87"}],"publist_id":"7769","title":"Mammalian mitochondrial complex I structure and disease causing mutations"},{"year":"2017","publication_status":"published","publication_identifier":{"isbn":["978-1-78262-865-1"]},"publication":"Mechanisms of primary energy transduction in biology ","language":[{"iso":"eng"}],"day":"29","page":"25 - 59","date_created":"2018-12-11T11:46:30Z","doi":"10.1039/9781788010405-00025","date_published":"2017-11-29T00:00:00Z","abstract":[{"lang":"eng","text":"Complex I (NADH:ubiquinone oxidoreductase) plays a central role in cellular energy generation, contributing to the proton motive force used to produce ATP. It couples the transfer of two electrons between NADH and quinone to translocation of four protons across the membrane. It is the largest protein assembly of bacterial and mitochondrial respiratory chains, composed, in mammals, of up to 45 subunits with a total molecular weight of ∼1 MDa. Bacterial enzyme is about half the size, providing the important “minimal” model of complex I. The l-shaped complex consists of a hydrophilic arm, where electron transfer occurs, and a membrane arm, where proton translocation takes place. Previously, we have solved the crystal structures of the hydrophilic domain of complex I from Thermus thermophilus and of the membrane domain from Escherichia coli, followed by the atomic structure of intact, entire complex I from T. thermophilus. Recently, we have solved by cryo-EM a first complete atomic structure of mammalian (ovine) mitochondrial complex I. Core subunits are well conserved from the bacterial version, whilst supernumerary subunits form an interlinked, stabilizing shell around the core. Subunits containing additional cofactors, including Zn ion, NADPH and phosphopantetheine, probably have regulatory roles. Dysfunction of mitochondrial complex I is implicated in many human neurodegenerative diseases. The structure of mammalian enzyme provides many insights into complex I mechanism, assembly, maturation and dysfunction, allowing detailed molecular analysis of disease-causing mutations."}],"oa_version":"None","publisher":"Royal Society of Chemistry","quality_controlled":"1","month":"11","citation":{"mla":"Sazanov, Leonid A. “Structure of Respiratory Complex I: ‘Minimal’ Bacterial and ‘de Luxe’ Mammalian Versions.” Mechanisms of Primary Energy Transduction in Biology , edited by Mårten Wikström, Royal Society of Chemistry, 2017, pp. 25–59, doi:10.1039/9781788010405-00025.","short":"L.A. Sazanov, in:, M. Wikström (Ed.), Mechanisms of Primary Energy Transduction in Biology , Royal Society of Chemistry, 2017, pp. 25–59.","ieee":"L. A. Sazanov, “Structure of respiratory complex I: ‘Minimal’ bacterial and ‘de luxe’ mammalian versions,” in Mechanisms of primary energy transduction in biology , M. Wikström, Ed. Royal Society of Chemistry, 2017, pp. 25–59.","ama":"Sazanov LA. Structure of respiratory complex I: “Minimal” bacterial and “de luxe” mammalian versions. In: Wikström M, ed. Mechanisms of Primary Energy Transduction in Biology . Mechanisms of Primary Energy Transduction in Biology . Royal Society of Chemistry; 2017:25-59. doi:10.1039/9781788010405-00025","apa":"Sazanov, L. A. (2017). Structure of respiratory complex I: “Minimal” bacterial and “de luxe” mammalian versions. In M. Wikström (Ed.), Mechanisms of primary energy transduction in biology (pp. 25–59). Royal Society of Chemistry. https://doi.org/10.1039/9781788010405-00025","chicago":"Sazanov, Leonid A. “Structure of Respiratory Complex I: ‘Minimal’ Bacterial and ‘de Luxe’ Mammalian Versions.” In Mechanisms of Primary Energy Transduction in Biology , edited by Mårten Wikström, 25–59. Mechanisms of Primary Energy Transduction in Biology . Royal Society of Chemistry, 2017. https://doi.org/10.1039/9781788010405-00025.","ista":"Sazanov LA. 2017.Structure of respiratory complex I: “Minimal” bacterial and “de luxe” mammalian versions. In: Mechanisms of primary energy transduction in biology . , 25–59."},"date_updated":"2021-01-12T07:56:59Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"last_name":"Sazanov","full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","first_name":"Leonid A"}],"publist_id":"7379","department":[{"_id":"LeSa"}],"editor":[{"full_name":"Wikström, Mårten","last_name":"Wikström","first_name":"Mårten"}],"title":"Structure of respiratory complex I: “Minimal” bacterial and “de luxe” mammalian versions","_id":"444","series_title":"Mechanisms of Primary Energy Transduction in Biology ","type":"book_chapter","status":"public"},{"author":[{"last_name":"Letts","orcid":"0000-0002-9864-3586","full_name":"Letts, James A","id":"322DA418-F248-11E8-B48F-1D18A9856A87","first_name":"James A"},{"first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989","last_name":"Sazanov"}],"publist_id":"7304","title":"Clarifying the supercomplex: The higher-order organization of the mitochondrial electron transport chain","citation":{"short":"J.A. Letts, L.A. Sazanov, Nature Structural and Molecular Biology 24 (2017) 800–808.","ieee":"J. A. Letts and L. A. Sazanov, “Clarifying the supercomplex: The higher-order organization of the mitochondrial electron transport chain,” Nature Structural and Molecular Biology, vol. 24, no. 10. Nature Publishing Group, pp. 800–808, 2017.","ama":"Letts JA, Sazanov LA. Clarifying the supercomplex: The higher-order organization of the mitochondrial electron transport chain. Nature Structural and Molecular Biology. 2017;24(10):800-808. doi:10.1038/nsmb.3460","apa":"Letts, J. A., & Sazanov, L. A. (2017). Clarifying the supercomplex: The higher-order organization of the mitochondrial electron transport chain. Nature Structural and Molecular Biology. Nature Publishing Group. https://doi.org/10.1038/nsmb.3460","mla":"Letts, James A., and Leonid A. Sazanov. “Clarifying the Supercomplex: The Higher-Order Organization of the Mitochondrial Electron Transport Chain.” Nature Structural and Molecular Biology, vol. 24, no. 10, Nature Publishing Group, 2017, pp. 800–08, doi:10.1038/nsmb.3460.","ista":"Letts JA, Sazanov LA. 2017. Clarifying the supercomplex: The higher-order organization of the mitochondrial electron transport chain. Nature Structural and Molecular Biology. 24(10), 800–808.","chicago":"Letts, James A, and Leonid A Sazanov. “Clarifying the Supercomplex: The Higher-Order Organization of the Mitochondrial Electron Transport Chain.” Nature Structural and Molecular Biology. Nature Publishing Group, 2017. https://doi.org/10.1038/nsmb.3460."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","project":[{"call_identifier":"H2020","_id":"2590DB08-B435-11E9-9278-68D0E5697425","grant_number":"701309","name":"Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes (H2020)"}],"page":"800 - 808","doi":"10.1038/nsmb.3460","date_published":"2017-10-05T00:00:00Z","date_created":"2018-12-11T11:46:54Z","has_accepted_license":"1","year":"2017","day":"05","publication":"Nature Structural and Molecular Biology","publisher":"Nature Publishing Group","quality_controlled":"1","oa":1,"department":[{"_id":"LeSa"}],"file_date_updated":"2020-07-14T12:46:36Z","date_updated":"2021-01-12T08:01:17Z","ddc":["572"],"type":"journal_article","article_type":"original","status":"public","_id":"515","volume":24,"issue":"10","ec_funded":1,"publication_identifier":{"issn":["15459993"]},"publication_status":"published","file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"9bc7e8c41b43636dd7566289e511f096","file_id":"6993","date_updated":"2020-07-14T12:46:36Z","file_size":4118385,"creator":"lsazanov","date_created":"2019-11-07T12:51:07Z","file_name":"29893_2_merged_1501257589_red.pdf"}],"language":[{"iso":"eng"}],"scopus_import":1,"month":"10","intvolume":" 24","abstract":[{"lang":"eng","text":"The oxidative phosphorylation electron transport chain (OXPHOS-ETC) of the inner mitochondrial membrane is composed of five large protein complexes, named CI-CV. These complexes convert energy from the food we eat into ATP, a small molecule used to power a multitude of essential reactions throughout the cell. OXPHOS-ETC complexes are organized into supercomplexes (SCs) of defined stoichiometry: CI forms a supercomplex with CIII2 and CIV (SC I+III2+IV, known as the respirasome), as well as with CIII2 alone (SC I+III2). CIII2 forms a supercomplex with CIV (SC III2+IV) and CV forms dimers (CV2). Recent cryo-EM studies have revealed the structures of SC I+III2+IV and SC I+III2. Furthermore, recent work has shed light on the assembly and function of the SCs. Here we review and compare these recent studies and discuss how they have advanced our understanding of mitochondrial electron transport."}],"oa_version":"Submitted Version"},{"article_number":"38094","citation":{"ieee":"J. Gutierrez-Fernandez et al., “Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis,” Scientific Reports, vol. 6. Nature Publishing Group, 2016.","short":"J. Gutierrez-Fernandez, M. Saleh, M. Alcorlo, A. Gómez Mejóa, D. Pantoja Uceda, M. Treviño, F. Vob, M. Abdullah, S. Galán Bartual, J. Seinen, P. Sánchez Murcia, F. Gago, M. Bruix, S. Hammerschmidt, J. Hermoso, Scientific Reports 6 (2016).","ama":"Gutierrez-Fernandez J, Saleh M, Alcorlo M, et al. Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis. Scientific Reports. 2016;6. doi:10.1038/srep38094","apa":"Gutierrez-Fernandez, J., Saleh, M., Alcorlo, M., Gómez Mejóa, A., Pantoja Uceda, D., Treviño, M., … Hermoso, J. (2016). Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis. Scientific Reports. Nature Publishing Group. https://doi.org/10.1038/srep38094","mla":"Gutierrez-Fernandez, Javier, et al. “Modular Architecture and Unique Teichoic Acid Recognition Features of Choline-Binding Protein L CbpL Contributing to Pneumococcal Pathogenesis.” Scientific Reports, vol. 6, 38094, Nature Publishing Group, 2016, doi:10.1038/srep38094.","ista":"Gutierrez-Fernandez J, Saleh M, Alcorlo M, Gómez Mejóa A, Pantoja Uceda D, Treviño M, Vob F, Abdullah M, Galán Bartual S, Seinen J, Sánchez Murcia P, Gago F, Bruix M, Hammerschmidt S, Hermoso J. 2016. Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis. Scientific Reports. 6, 38094.","chicago":"Gutierrez-Fernandez, Javier, Malek Saleh, Martín Alcorlo, Alejandro Gómez Mejóa, David Pantoja Uceda, Miguel Treviño, Franziska Vob, et al. “Modular Architecture and Unique Teichoic Acid Recognition Features of Choline-Binding Protein L CbpL Contributing to Pneumococcal Pathogenesis.” Scientific Reports. Nature Publishing Group, 2016. https://doi.org/10.1038/srep38094."},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","author":[{"full_name":"Gutierrez-Fernandez, Javier","last_name":"Gutierrez-Fernandez","first_name":"Javier","id":"3D9511BA-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Malek","full_name":"Saleh, Malek","last_name":"Saleh"},{"first_name":"Martín","last_name":"Alcorlo","full_name":"Alcorlo, Martín"},{"first_name":"Alejandro","last_name":"Gómez Mejóa","full_name":"Gómez Mejóa, Alejandro"},{"first_name":"David","last_name":"Pantoja Uceda","full_name":"Pantoja Uceda, David"},{"first_name":"Miguel","full_name":"Treviño, Miguel","last_name":"Treviño"},{"first_name":"Franziska","last_name":"Vob","full_name":"Vob, Franziska"},{"first_name":"Mohammed","last_name":"Abdullah","full_name":"Abdullah, Mohammed"},{"first_name":"Sergio","full_name":"Galán Bartual, Sergio","last_name":"Galán Bartual"},{"first_name":"Jolien","last_name":"Seinen","full_name":"Seinen, Jolien"},{"full_name":"Sánchez Murcia, Pedro","last_name":"Sánchez Murcia","first_name":"Pedro"},{"first_name":"Federico","full_name":"Gago, Federico","last_name":"Gago"},{"first_name":"Marta","full_name":"Bruix, Marta","last_name":"Bruix"},{"full_name":"Hammerschmidt, Sven","last_name":"Hammerschmidt","first_name":"Sven"},{"full_name":"Hermoso, Juan","last_name":"Hermoso","first_name":"Juan"}],"publist_id":"6167","title":"Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis","acknowledgement":"We gratefully acknowledge Karsta Barnekow and Kristine Sievert-Giermann, for technical assistance and Lothar Petruschka for in silico analysis (all Dept. of Genetics, University of Greifswald). We are further grateful to the staff from SLS synchrotron beamline for help in data collection. This work was supported by grants from the Deutsche Forschungsgemeinschaft DFG GRK 1870 (to SH) and the Spanish Ministry of Economy and Competitiveness (BFU2014-59389-P to JAH, CTQ2014-52633-P to MB and SAF2012-39760-C02-02 to FG) and S2010/BMD-2457 (Community of Madrid to JAH and FG).","oa":1,"publisher":"Nature Publishing Group","quality_controlled":"1","year":"2016","has_accepted_license":"1","publication":"Scientific Reports","day":"05","date_created":"2018-12-11T11:50:36Z","doi":"10.1038/srep38094","date_published":"2016-12-05T00:00:00Z","_id":"1186","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","pubrep_id":"735","status":"public","date_updated":"2021-01-12T06:48:56Z","ddc":["576","610"],"department":[{"_id":"LeSa"}],"file_date_updated":"2020-07-14T12:44:37Z","abstract":[{"lang":"eng","text":"The human pathogen Streptococcus pneumoniae is decorated with a special class of surface-proteins known as choline-binding proteins (CBPs) attached to phosphorylcholine (PCho) moieties from cell-wall teichoic acids. By a combination of X-ray crystallography, NMR, molecular dynamics techniques and in vivo virulence and phagocytosis studies, we provide structural information of choline-binding protein L (CbpL) and demonstrate its impact on pneumococcal pathogenesis and immune evasion. CbpL is a very elongated three-module protein composed of (i) an Excalibur Ca 2+ -binding domain -reported in this work for the very first time-, (ii) an unprecedented anchorage module showing alternate disposition of canonical and non-canonical choline-binding sites that allows vine-like binding of fully-PCho-substituted teichoic acids (with two choline moieties per unit), and (iii) a Ltp-Lipoprotein domain. Our structural and infection assays indicate an important role of the whole multimodular protein allowing both to locate CbpL at specific places on the cell wall and to interact with host components in order to facilitate pneumococcal lung infection and transmigration from nasopharynx to the lungs and blood. CbpL implication in both resistance against killing by phagocytes and pneumococcal pathogenesis further postulate this surface-protein as relevant among the pathogenic arsenal of the pneumococcus."}],"oa_version":"Published Version","scopus_import":1,"intvolume":" 6","month":"12","publication_status":"published","language":[{"iso":"eng"}],"file":[{"relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_id":"4804","checksum":"e007d78b483bc59bf5ab98e9d42a6ec1","creator":"system","file_size":2716045,"date_updated":"2020-07-14T12:44:37Z","file_name":"IST-2017-735-v1+1_srep38094.pdf","date_created":"2018-12-12T10:10:18Z"}],"volume":6},{"project":[{"_id":"2593EBD6-B435-11E9-9278-68D0E5697425","name":"Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes (FEBS)"},{"_id":"2590DB08-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes (H2020)","grant_number":"701309"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"ieee":"J. A. Letts, G. Degliesposti, K. Fiedorczuk, M. Skehel, and L. A. Sazanov, “Purification of ovine respiratory complex i results in a highly active and stable preparation,” Journal of Biological Chemistry, vol. 291, no. 47. American Society for Biochemistry and Molecular Biology, pp. 24657–24675, 2016.","short":"J.A. Letts, G. Degliesposti, K. Fiedorczuk, M. Skehel, L.A. Sazanov, Journal of Biological Chemistry 291 (2016) 24657–24675.","apa":"Letts, J. A., Degliesposti, G., Fiedorczuk, K., Skehel, M., & Sazanov, L. A. (2016). Purification of ovine respiratory complex i results in a highly active and stable preparation. Journal of Biological Chemistry. American Society for Biochemistry and Molecular Biology. https://doi.org/10.1074/jbc.M116.735142","ama":"Letts JA, Degliesposti G, Fiedorczuk K, Skehel M, Sazanov LA. Purification of ovine respiratory complex i results in a highly active and stable preparation. Journal of Biological Chemistry. 2016;291(47):24657-24675. doi:10.1074/jbc.M116.735142","mla":"Letts, James A., et al. “Purification of Ovine Respiratory Complex i Results in a Highly Active and Stable Preparation.” Journal of Biological Chemistry, vol. 291, no. 47, American Society for Biochemistry and Molecular Biology, 2016, pp. 24657–75, doi:10.1074/jbc.M116.735142.","ista":"Letts JA, Degliesposti G, Fiedorczuk K, Skehel M, Sazanov LA. 2016. Purification of ovine respiratory complex i results in a highly active and stable preparation. Journal of Biological Chemistry. 291(47), 24657–24675.","chicago":"Letts, James A, Gianluca Degliesposti, Karol Fiedorczuk, Mark Skehel, and Leonid A Sazanov. “Purification of Ovine Respiratory Complex i Results in a Highly Active and Stable Preparation.” Journal of Biological Chemistry. American Society for Biochemistry and Molecular Biology, 2016. https://doi.org/10.1074/jbc.M116.735142."},"title":"Purification of ovine respiratory complex i results in a highly active and stable preparation","author":[{"first_name":"James A","id":"322DA418-F248-11E8-B48F-1D18A9856A87","last_name":"Letts","orcid":"0000-0002-9864-3586","full_name":"Letts, James A"},{"first_name":"Gianluca","full_name":"Degliesposti, Gianluca","last_name":"Degliesposti"},{"id":"5BFF67CE-02D1-11E9-B11A-A5A4D7DFFFD0","first_name":"Karol","last_name":"Fiedorczuk","full_name":"Fiedorczuk, Karol"},{"last_name":"Skehel","full_name":"Skehel, Mark","first_name":"Mark"},{"orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","last_name":"Sazanov","first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87"}],"publist_id":"6139","acknowledgement":"J.A.S supported in part by a Medical Research D.G.Council UK Ph.D. fellowship.\r\nThis work was supported in part by European Union's 2020 Research and Innovation Program under Grant 701309. \r\n","oa":1,"publisher":"American Society for Biochemistry and Molecular Biology","quality_controlled":"1","publication":"Journal of Biological Chemistry","day":"18","year":"2016","date_created":"2018-12-11T11:50:44Z","date_published":"2016-11-18T00:00:00Z","doi":"10.1074/jbc.M116.735142","page":"24657 - 24675","_id":"1209","status":"public","type":"journal_article","date_updated":"2021-01-12T06:49:06Z","department":[{"_id":"LeSa"}],"oa_version":"Submitted Version","abstract":[{"text":"NADH-ubiquinone oxidoreductase (complex I) is the largest (∼1 MDa) and the least characterized complex of the mitochondrial electron transport chain. Because of the ease of sample availability, previous work has focused almost exclusively on bovine complex I. However, only medium resolution structural analyses of this complex have been reported. Working with other mammalian complex I homologues is a potential approach for overcoming these limitations. Due to the inherent difficulty of expressing large membrane protein complexes, screening of complex I homologues is limited to large mammals reared for human consumption. The high sequence identity among these available sources may preclude the benefits of screening. Here, we report the characterization of complex I purified from Ovis aries (ovine) heart mitochondria. All 44 unique subunits of the intact complex were identified by mass spectrometry. We identified differences in the subunit composition of subcomplexes of ovine complex I as compared with bovine, suggesting differential stability of inter-subunit interactions within the complex. Furthermore, the 42-kDa subunit, which is easily lost from the bovine enzyme, remains tightly bound to ovine complex I. Additionally, we developed a novel purification protocol for highly active and stable mitochondrial complex I using the branched-chain detergent lauryl maltose neopentyl glycol. Our data demonstrate that, although closely related, significant differences exist between the biochemical properties of complex I prepared from ovine and bovine mitochondria and that ovine complex I represents a suitable alternative target for further structural studies. ","lang":"eng"}],"intvolume":" 291","month":"11","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114416/","open_access":"1"}],"scopus_import":1,"language":[{"iso":"eng"}],"publication_status":"published","ec_funded":1,"issue":"47","volume":291},{"ec_funded":1,"volume":538,"issue":"7625","publication_status":"published","language":[{"iso":"eng"}],"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5164932/","open_access":"1"}],"scopus_import":1,"intvolume":" 538","month":"10","abstract":[{"lang":"eng","text":"Mitochondrial complex I (also known as NADH:ubiquinone oxidoreductase) contributes to cellular energy production by transferring electrons from NADH to ubiquinone coupled to proton translocation across the membrane. It is the largest protein assembly of the respiratory chain with a total mass of 970 kilodaltons. Here we present a nearly complete atomic structure of ovine (Ovis aries) mitochondrial complex I at 3.9 Å resolution, solved by cryo-electron microscopy with cross-linking and mass-spectrometry mapping experiments. All 14 conserved core subunits and 31 mitochondria-specific supernumerary subunits are resolved within the L-shaped molecule. The hydrophilic matrix arm comprises flavin mononucleotide and 8 iron-sulfur clusters involved in electron transfer, and the membrane arm contains 78 transmembrane helices, mostly contributed by antiporter-like subunits involved in proton translocation. Supernumerary subunits form an interlinked, stabilizing shell around the conserved core. Tightly bound lipids (including cardiolipins) further stabilize interactions between the hydrophobic subunits. Subunits with possible regulatory roles contain additional cofactors, NADPH and two phosphopantetheine molecules, which are shown to be involved in inter-subunit interactions. We observe two different conformations of the complex, which may be related to the conformationally driven coupling mechanism and to the active-deactive transition of the enzyme. Our structure provides insight into the mechanism, assembly, maturation and dysfunction of mitochondrial complex I, and allows detailed molecular analysis of disease-causing mutations."}],"pmid":1,"oa_version":"Submitted Version","department":[{"_id":"LeSa"}],"date_updated":"2021-01-12T06:49:13Z","type":"journal_article","article_type":"original","status":"public","_id":"1226","page":"406 - 410","date_created":"2018-12-11T11:50:49Z","doi":"10.1038/nature19794","date_published":"2016-10-20T00:00:00Z","year":"2016","publication":"Nature","day":"20","oa":1,"quality_controlled":"1","publisher":"Nature Publishing Group","article_processing_charge":"No","external_id":{"pmid":["27595392"]},"author":[{"last_name":"Fiedorczuk","full_name":"Fiedorczuk, Karol","first_name":"Karol","id":"5BFF67CE-02D1-11E9-B11A-A5A4D7DFFFD0"},{"id":"322DA418-F248-11E8-B48F-1D18A9856A87","first_name":"James A","full_name":"Letts, James A","orcid":"0000-0002-9864-3586","last_name":"Letts"},{"first_name":"Gianluca","last_name":"Degliesposti","full_name":"Degliesposti, Gianluca"},{"id":"3FDF9472-F248-11E8-B48F-1D18A9856A87","first_name":"Karol","last_name":"Kaszuba","full_name":"Kaszuba, Karol"},{"first_name":"Mark","last_name":"Skehel","full_name":"Skehel, Mark"},{"last_name":"Sazanov","full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989","first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87"}],"publist_id":"6108","title":"Atomic structure of the entire mammalian mitochondrial complex i","citation":{"ieee":"K. Fiedorczuk, J. A. Letts, G. Degliesposti, K. Kaszuba, M. Skehel, and L. A. Sazanov, “Atomic structure of the entire mammalian mitochondrial complex i,” Nature, vol. 538, no. 7625. Nature Publishing Group, pp. 406–410, 2016.","short":"K. Fiedorczuk, J.A. Letts, G. Degliesposti, K. Kaszuba, M. Skehel, L.A. Sazanov, Nature 538 (2016) 406–410.","apa":"Fiedorczuk, K., Letts, J. A., Degliesposti, G., Kaszuba, K., Skehel, M., & Sazanov, L. A. (2016). Atomic structure of the entire mammalian mitochondrial complex i. Nature. Nature Publishing Group. https://doi.org/10.1038/nature19794","ama":"Fiedorczuk K, Letts JA, Degliesposti G, Kaszuba K, Skehel M, Sazanov LA. Atomic structure of the entire mammalian mitochondrial complex i. Nature. 2016;538(7625):406-410. doi:10.1038/nature19794","mla":"Fiedorczuk, Karol, et al. “Atomic Structure of the Entire Mammalian Mitochondrial Complex I.” Nature, vol. 538, no. 7625, Nature Publishing Group, 2016, pp. 406–10, doi:10.1038/nature19794.","ista":"Fiedorczuk K, Letts JA, Degliesposti G, Kaszuba K, Skehel M, Sazanov LA. 2016. Atomic structure of the entire mammalian mitochondrial complex i. Nature. 538(7625), 406–410.","chicago":"Fiedorczuk, Karol, James A Letts, Gianluca Degliesposti, Karol Kaszuba, Mark Skehel, and Leonid A Sazanov. “Atomic Structure of the Entire Mammalian Mitochondrial Complex I.” Nature. Nature Publishing Group, 2016. https://doi.org/10.1038/nature19794."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","project":[{"name":"Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes (FEBS)","_id":"2593EBD6-B435-11E9-9278-68D0E5697425"},{"_id":"2590DB08-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"701309","name":"Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes (H2020)"}]},{"day":"29","publication":"Nature","language":[{"iso":"eng"}],"publication_status":"published","year":"2016","date_published":"2016-09-29T00:00:00Z","issue":"7622","volume":537,"doi":"10.1038/nature19774","date_created":"2018-12-11T11:50:51Z","page":"644 - 648","oa_version":"None","acknowledgement":"We thank the MRC LMB Cambridge for the use of the Titan Krios microscope. Data processing was performed using the IST high-performance computer cluster. J.A.L. holds a long-term fellowship from FEBS. K.F. is partially funded by a MRC UK PhD fellowship.","abstract":[{"text":"Mitochondrial electron transport chain complexes are organized into supercomplexes responsible for carrying out cellular respiration. Here we present three architectures of mammalian (ovine) supercomplexes determined by cryo-electron microscopy. We identify two distinct arrangements of supercomplex CICIII 2 CIV (the respirasome) - a major 'tight' form and a minor 'loose' form (resolved at the resolution of 5.8 Å and 6.7 Å, respectively), which may represent different stages in supercomplex assembly or disassembly. We have also determined an architecture of supercomplex CICIII 2 at 7.8 Å resolution. All observed density can be attributed to the known 80 subunits of the individual complexes, including 132 transmembrane helices. The individual complexes form tight interactions that vary between the architectures, with complex IV subunit COX7a switching contact from complex III to complex I. The arrangement of active sites within the supercomplex may help control reactive oxygen species production. To our knowledge, these are the first complete architectures of the dominant, physiologically relevant state of the electron transport chain.","lang":"eng"}],"month":"09","intvolume":" 537","publisher":"Nature Publishing Group","quality_controlled":"1","scopus_import":1,"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","date_updated":"2021-01-12T06:49:16Z","citation":{"ista":"Letts JA, Fiedorczuk K, Sazanov LA. 2016. The architecture of respiratory supercomplexes. Nature. 537(7622), 644–648.","chicago":"Letts, James A, Karol Fiedorczuk, and Leonid A Sazanov. “The Architecture of Respiratory Supercomplexes.” Nature. Nature Publishing Group, 2016. https://doi.org/10.1038/nature19774.","apa":"Letts, J. A., Fiedorczuk, K., & Sazanov, L. A. (2016). The architecture of respiratory supercomplexes. Nature. Nature Publishing Group. https://doi.org/10.1038/nature19774","ama":"Letts JA, Fiedorczuk K, Sazanov LA. The architecture of respiratory supercomplexes. Nature. 2016;537(7622):644-648. doi:10.1038/nature19774","short":"J.A. Letts, K. Fiedorczuk, L.A. Sazanov, Nature 537 (2016) 644–648.","ieee":"J. A. Letts, K. Fiedorczuk, and L. A. Sazanov, “The architecture of respiratory supercomplexes,” Nature, vol. 537, no. 7622. Nature Publishing Group, pp. 644–648, 2016.","mla":"Letts, James A., et al. “The Architecture of Respiratory Supercomplexes.” Nature, vol. 537, no. 7622, Nature Publishing Group, 2016, pp. 644–48, doi:10.1038/nature19774."},"department":[{"_id":"LeSa"}],"title":"The architecture of respiratory supercomplexes","author":[{"first_name":"James A","id":"322DA418-F248-11E8-B48F-1D18A9856A87","last_name":"Letts","full_name":"Letts, James A","orcid":"0000-0002-9864-3586"},{"last_name":"Fiedorczuk","full_name":"Fiedorczuk, Karol","id":"5BFF67CE-02D1-11E9-B11A-A5A4D7DFFFD0","first_name":"Karol"},{"last_name":"Sazanov","full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989","first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87"}],"publist_id":"6102","_id":"1232","project":[{"_id":"2593EBD6-B435-11E9-9278-68D0E5697425","name":"Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes (FEBS)"}],"status":"public","type":"journal_article"},{"article_number":"33607","title":"Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex","publist_id":"6040","author":[{"full_name":"Postila, Pekka","last_name":"Postila","first_name":"Pekka"},{"id":"3FDF9472-F248-11E8-B48F-1D18A9856A87","first_name":"Karol","full_name":"Kaszuba, Karol","last_name":"Kaszuba"},{"first_name":"Patryk","last_name":"Kuleta","full_name":"Kuleta, Patryk"},{"last_name":"Vattulainen","full_name":"Vattulainen, Ilpo","first_name":"Ilpo"},{"full_name":"Sarewicz, Marcin","last_name":"Sarewicz","first_name":"Marcin"},{"first_name":"Artur","last_name":"Osyczka","full_name":"Osyczka, Artur"},{"first_name":"Tomasz","full_name":"Róg, Tomasz","last_name":"Róg"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Postila P, Kaszuba K, Kuleta P, Vattulainen I, Sarewicz M, Osyczka A, Róg T. 2016. Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex. Scientific Reports. 6, 33607.","chicago":"Postila, Pekka, Karol Kaszuba, Patryk Kuleta, Ilpo Vattulainen, Marcin Sarewicz, Artur Osyczka, and Tomasz Róg. “Atomistic Determinants of Co-Enzyme Q Reduction at the Qi-Site of the Cytochrome Bc1 Complex.” Scientific Reports. Nature Publishing Group, 2016. https://doi.org/10.1038/srep33607.","apa":"Postila, P., Kaszuba, K., Kuleta, P., Vattulainen, I., Sarewicz, M., Osyczka, A., & Róg, T. (2016). Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex. Scientific Reports. Nature Publishing Group. https://doi.org/10.1038/srep33607","ama":"Postila P, Kaszuba K, Kuleta P, et al. Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex. Scientific Reports. 2016;6. doi:10.1038/srep33607","ieee":"P. Postila et al., “Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex,” Scientific Reports, vol. 6. Nature Publishing Group, 2016.","short":"P. Postila, K. Kaszuba, P. Kuleta, I. Vattulainen, M. Sarewicz, A. Osyczka, T. Róg, Scientific Reports 6 (2016).","mla":"Postila, Pekka, et al. “Atomistic Determinants of Co-Enzyme Q Reduction at the Qi-Site of the Cytochrome Bc1 Complex.” Scientific Reports, vol. 6, 33607, Nature Publishing Group, 2016, doi:10.1038/srep33607."},"quality_controlled":"1","publisher":"Nature Publishing Group","oa":1,"acknowledgement":"We wish to thank CSC – IT Centre for Science (Espoo, Finland) for computational resources. For financial support, we wish to thank the Academy of Finland (TR, IV and PAP; Center of Excellence in Biomembrane Research (IV, TR)), the Finnish Doctoral Programme in Computational Sciences (KK), the Sigrid Juselius Foundation (IV), the Paulo Foundation (PAP), and the European Research Council (IV, TR; Advanced Grant project CROWDED-PRO-LIPIDS). AO acknowledges The Wellcome Trust International Senior Research Fellowship.","date_published":"2016-09-26T00:00:00Z","doi":"10.1038/srep33607","date_created":"2018-12-11T11:51:05Z","day":"26","publication":"Scientific Reports","has_accepted_license":"1","year":"2016","status":"public","pubrep_id":"691","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"1276","department":[{"_id":"LeSa"}],"file_date_updated":"2020-07-14T12:44:42Z","ddc":["576"],"date_updated":"2021-01-12T06:49:34Z","month":"09","intvolume":" 6","scopus_import":1,"oa_version":"Published Version","abstract":[{"text":"The cytochrome (cyt) bc 1 complex is an integral component of the respiratory electron transfer chain sustaining the energy needs of organisms ranging from humans to bacteria. Due to its ubiquitous role in the energy metabolism, both the oxidation and reduction of the enzyme's substrate co-enzyme Q has been studied vigorously. Here, this vast amount of data is reassessed after probing the substrate reduction steps at the Q i-site of the cyt bc 1 complex of Rhodobacter capsulatus using atomistic molecular dynamics simulations. The simulations suggest that the Lys251 side chain could rotate into the Q i-site to facilitate binding of half-protonated semiquinone-a reaction intermediate that is potentially formed during substrate reduction. At this bent pose, the Lys251 forms a salt bridge with the Asp252, thus making direct proton transfer possible. In the neutral state, the lysine side chain stays close to the conserved binding location of cardiolipin (CL). This back-and-forth motion between the CL and Asp252 indicates that Lys251 functions as a proton shuttle controlled by pH-dependent negative feedback. The CL/K/D switching, which represents a refinement to the previously described CL/K pathway, fine-tunes the proton transfer process. Lastly, the simulation data was used to formulate a mechanism for reducing the substrate at the Q i-site.","lang":"eng"}],"volume":6,"file":[{"relation":"main_file","access_level":"open_access","content_type":"application/pdf","checksum":"07c591c1250ebef266333cbc3228b4dd","file_id":"5261","creator":"system","file_size":1960563,"date_updated":"2020-07-14T12:44:42Z","file_name":"IST-2016-691-v1+1_srep33607.pdf","date_created":"2018-12-12T10:17:09Z"}],"language":[{"iso":"eng"}],"publication_status":"published"},{"status":"public","type":"journal_article","_id":"1288","department":[{"_id":"LeSa"}],"title":"Reversible FMN dissociation from Escherichia coli respiratory complex I","author":[{"full_name":"Holt, Peter","last_name":"Holt","first_name":"Peter"},{"full_name":"Efremov, Rouslan","last_name":"Efremov","first_name":"Rouslan"},{"first_name":"Eiko","full_name":"Nakamaru Ogiso, Eiko","last_name":"Nakamaru Ogiso"},{"orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","last_name":"Sazanov","first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87"}],"publist_id":"6028","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","date_updated":"2021-01-12T06:49:38Z","citation":{"mla":"Holt, Peter, et al. “Reversible FMN Dissociation from Escherichia Coli Respiratory Complex I.” Biochimica et Biophysica Acta - Bioenergetics, vol. 1857, no. 11, Elsevier, 2016, pp. 1777–85, doi:10.1016/j.bbabio.2016.08.008.","ama":"Holt P, Efremov R, Nakamaru Ogiso E, Sazanov LA. Reversible FMN dissociation from Escherichia coli respiratory complex I. Biochimica et Biophysica Acta - Bioenergetics. 2016;1857(11):1777-1785. doi:10.1016/j.bbabio.2016.08.008","apa":"Holt, P., Efremov, R., Nakamaru Ogiso, E., & Sazanov, L. A. (2016). Reversible FMN dissociation from Escherichia coli respiratory complex I. Biochimica et Biophysica Acta - Bioenergetics. Elsevier. https://doi.org/10.1016/j.bbabio.2016.08.008","ieee":"P. Holt, R. Efremov, E. Nakamaru Ogiso, and L. A. Sazanov, “Reversible FMN dissociation from Escherichia coli respiratory complex I,” Biochimica et Biophysica Acta - Bioenergetics, vol. 1857, no. 11. Elsevier, pp. 1777–1785, 2016.","short":"P. Holt, R. Efremov, E. Nakamaru Ogiso, L.A. Sazanov, Biochimica et Biophysica Acta - Bioenergetics 1857 (2016) 1777–1785.","chicago":"Holt, Peter, Rouslan Efremov, Eiko Nakamaru Ogiso, and Leonid A Sazanov. “Reversible FMN Dissociation from Escherichia Coli Respiratory Complex I.” Biochimica et Biophysica Acta - Bioenergetics. Elsevier, 2016. https://doi.org/10.1016/j.bbabio.2016.08.008.","ista":"Holt P, Efremov R, Nakamaru Ogiso E, Sazanov LA. 2016. Reversible FMN dissociation from Escherichia coli respiratory complex I. Biochimica et Biophysica Acta - Bioenergetics. 1857(11), 1777–1785."},"intvolume":" 1857","month":"11","quality_controlled":"1","scopus_import":1,"publisher":"Elsevier","acknowledgement":"This work was funded by the UK Medical Research Council.","oa_version":"None","abstract":[{"text":"Respiratory complex I transfers electrons from NADH to quinone, utilizing the reaction energy to translocate protons across the membrane. It is a key enzyme of the respiratory chain of many prokaryotic and most eukaryotic organisms. The reversible NADH oxidation reaction is facilitated in complex I by non-covalently bound flavin mononucleotide (FMN). Here we report that the catalytic activity of E. coli complex I with artificial electron acceptors potassium ferricyanide (FeCy) and hexaamineruthenium (HAR) is significantly inhibited in the enzyme pre-reduced by NADH. Further, we demonstrate that the inhibition is caused by reversible dissociation of FMN. The binding constant (Kd) for FMN increases from the femto- or picomolar range in oxidized complex I to the nanomolar range in the NADH reduced enzyme, with an FMN dissociation time constant of ~ 5 s. The oxidation state of complex I, rather than that of FMN, proved critical to the dissociation. Such dissociation is not observed with the T. thermophilus enzyme and our analysis suggests that the difference may be due to the unusually high redox potential of Fe-S cluster N1a in E. coli. It is possible that the enzyme attenuates ROS production in vivo by releasing FMN under highly reducing conditions.","lang":"eng"}],"date_created":"2018-12-11T11:51:09Z","volume":1857,"issue":"11","date_published":"2016-11-01T00:00:00Z","doi":"10.1016/j.bbabio.2016.08.008","page":"1777 - 1785","publication":"Biochimica et Biophysica Acta - Bioenergetics","language":[{"iso":"eng"}],"day":"01","publication_status":"published","year":"2016"},{"_id":"1521","status":"public","type":"journal_article","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","date_updated":"2021-01-12T06:51:21Z","citation":{"mla":"Berrisford, John, et al. “Structure of Bacterial Respiratory Complex I.” Biochimica et Biophysica Acta - Bioenergetics, vol. 1857, no. 7, Elsevier, 2016, pp. 892–901, doi:10.1016/j.bbabio.2016.01.012.","apa":"Berrisford, J., Baradaran, R., & Sazanov, L. A. (2016). Structure of bacterial respiratory complex I. Biochimica et Biophysica Acta - Bioenergetics. Elsevier. https://doi.org/10.1016/j.bbabio.2016.01.012","ama":"Berrisford J, Baradaran R, Sazanov LA. Structure of bacterial respiratory complex I. Biochimica et Biophysica Acta - Bioenergetics. 2016;1857(7):892-901. doi:10.1016/j.bbabio.2016.01.012","short":"J. Berrisford, R. Baradaran, L.A. Sazanov, Biochimica et Biophysica Acta - Bioenergetics 1857 (2016) 892–901.","ieee":"J. Berrisford, R. Baradaran, and L. A. Sazanov, “Structure of bacterial respiratory complex I,” Biochimica et Biophysica Acta - Bioenergetics, vol. 1857, no. 7. Elsevier, pp. 892–901, 2016.","chicago":"Berrisford, John, Rozbeh Baradaran, and Leonid A Sazanov. “Structure of Bacterial Respiratory Complex I.” Biochimica et Biophysica Acta - Bioenergetics. Elsevier, 2016. https://doi.org/10.1016/j.bbabio.2016.01.012.","ista":"Berrisford J, Baradaran R, Sazanov LA. 2016. Structure of bacterial respiratory complex I. Biochimica et Biophysica Acta - Bioenergetics. 1857(7), 892–901."},"title":"Structure of bacterial respiratory complex I","department":[{"_id":"LeSa"}],"publist_id":"5654","author":[{"first_name":"John","last_name":"Berrisford","full_name":"Berrisford, John"},{"last_name":"Baradaran","full_name":"Baradaran, Rozbeh","first_name":"Rozbeh"},{"orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","last_name":"Sazanov","first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87"}],"oa_version":"None","acknowledgement":"funded by the Medical Research Council (Grant number MC_U105674180)","abstract":[{"text":"Complex I (NADH:ubiquinone oxidoreductase) plays a central role in cellular energy production, coupling electron transfer between NADH and quinone to proton translocation. It is the largest protein assembly of respiratory chains and one of the most elaborate redox membrane proteins known. Bacterial enzyme is about half the size of mitochondrial and thus provides its important "minimal" model. Dysfunction of mitochondrial complex I is implicated in many human neurodegenerative diseases. The L-shaped complex consists of a hydrophilic arm, where electron transfer occurs, and a membrane arm, where proton translocation takes place. We have solved the crystal structures of the hydrophilic domain of complex I from Thermus thermophilus, the membrane domain from Escherichia coli and recently of the intact, entire complex I from T. thermophilus (536. kDa, 16 subunits, 9 iron-sulphur clusters, 64 transmembrane helices). The 95. Å long electron transfer pathway through the enzyme proceeds from the primary electron acceptor flavin mononucleotide through seven conserved Fe-S clusters to the unusual elongated quinone-binding site at the interface with the membrane domain. Four putative proton translocation channels are found in the membrane domain, all linked by the central flexible axis containing charged residues. The redox energy of electron transfer is coupled to proton translocation by the as yet undefined mechanism proposed to involve long-range conformational changes. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt.","lang":"eng"}],"month":"07","intvolume":" 1857","quality_controlled":"1","scopus_import":1,"publisher":"Elsevier","day":"01","publication":"Biochimica et Biophysica Acta - Bioenergetics","language":[{"iso":"eng"}],"publication_status":"published","year":"2016","issue":"7","doi":"10.1016/j.bbabio.2016.01.012","date_published":"2016-07-01T00:00:00Z","volume":1857,"date_created":"2018-12-11T11:52:30Z","page":"892 - 901"},{"quality_controlled":"1","scopus_import":1,"publisher":"Nature Publishing Group","month":"05","intvolume":" 16","abstract":[{"text":"The mitochondrial respiratory chain, also known as the electron transport chain (ETC), is crucial to life, and energy production in the form of ATP is the main mitochondrial function. Three proton-translocating enzymes of the ETC, namely complexes I, III and IV, generate proton motive force, which in turn drives ATP synthase (complex V). The atomic structures and basic mechanisms of most respiratory complexes have previously been established, with the exception of complex I, the largest complex in the ETC. Recently, the crystal structure of the entire complex I was solved using a bacterial enzyme. The structure provided novel insights into the core architecture of the complex, the electron transfer and proton translocation pathways, as well as the mechanism that couples these two processes.","lang":"eng"}],"oa_version":"None","page":"375 - 388","doi":"10.1038/nrm3997","volume":16,"issue":"6","date_published":"2015-05-22T00:00:00Z","date_created":"2018-12-11T11:53:11Z","year":"2015","publication_status":"published","day":"22","language":[{"iso":"eng"}],"publication":"Nature Reviews Molecular Cell Biology","type":"journal_article","status":"public","_id":"1638","author":[{"first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","last_name":"Sazanov","full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989"}],"publist_id":"5517","title":"A giant molecular proton pump: structure and mechanism of respiratory complex I","department":[{"_id":"LeSa"}],"date_updated":"2021-01-12T06:52:10Z","citation":{"mla":"Sazanov, Leonid A. “A Giant Molecular Proton Pump: Structure and Mechanism of Respiratory Complex I.” Nature Reviews Molecular Cell Biology, vol. 16, no. 6, Nature Publishing Group, 2015, pp. 375–88, doi:10.1038/nrm3997.","apa":"Sazanov, L. A. (2015). A giant molecular proton pump: structure and mechanism of respiratory complex I. Nature Reviews Molecular Cell Biology. Nature Publishing Group. https://doi.org/10.1038/nrm3997","ama":"Sazanov LA. A giant molecular proton pump: structure and mechanism of respiratory complex I. Nature Reviews Molecular Cell Biology. 2015;16(6):375-388. doi:10.1038/nrm3997","ieee":"L. A. Sazanov, “A giant molecular proton pump: structure and mechanism of respiratory complex I,” Nature Reviews Molecular Cell Biology, vol. 16, no. 6. Nature Publishing Group, pp. 375–388, 2015.","short":"L.A. Sazanov, Nature Reviews Molecular Cell Biology 16 (2015) 375–388.","chicago":"Sazanov, Leonid A. “A Giant Molecular Proton Pump: Structure and Mechanism of Respiratory Complex I.” Nature Reviews Molecular Cell Biology. Nature Publishing Group, 2015. https://doi.org/10.1038/nrm3997.","ista":"Sazanov LA. 2015. A giant molecular proton pump: structure and mechanism of respiratory complex I. Nature Reviews Molecular Cell Biology. 16(6), 375–388."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"oa_version":"None","abstract":[{"text":"The 1 MDa, 45-subunit proton-pumping NADH-ubiquinone oxidoreductase (complex I) is the largest complex of the mitochondrial electron transport chain. The molecular mechanism of complex I is central to the metabolism of cells, but has yet to be fully characterized. The last two years have seen steady progress towards this goal with the first atomic-resolution structure of the entire bacterial complex I, a 5 Å cryo-electron microscopy map of bovine mitochondrial complex I and a ∼3.8 Å resolution X-ray crystallographic study of mitochondrial complex I from yeast Yarrowia lipotytica. In this review we will discuss what we have learned from these studies and what remains to be elucidated.","lang":"eng"}],"intvolume":" 33","month":"08","quality_controlled":"1","scopus_import":1,"publisher":"Elsevier","language":[{"iso":"eng"}],"publication":"Current Opinion in Structural Biology","day":"01","year":"2015","publication_status":"published","date_created":"2018-12-11T11:53:27Z","doi":"10.1016/j.sbi.2015.08.008","issue":"8","volume":33,"date_published":"2015-08-01T00:00:00Z","page":"135 - 145","_id":"1683","status":"public","type":"journal_article","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"chicago":"Letts, James A, and Leonid A Sazanov. “Gaining Mass: The Structure of Respiratory Complex I-from Bacterial towards Mitochondrial Versions.” Current Opinion in Structural Biology. Elsevier, 2015. https://doi.org/10.1016/j.sbi.2015.08.008.","ista":"Letts JA, Sazanov LA. 2015. Gaining mass: The structure of respiratory complex I-from bacterial towards mitochondrial versions. Current Opinion in Structural Biology. 33(8), 135–145.","mla":"Letts, James A., and Leonid A. Sazanov. “Gaining Mass: The Structure of Respiratory Complex I-from Bacterial towards Mitochondrial Versions.” Current Opinion in Structural Biology, vol. 33, no. 8, Elsevier, 2015, pp. 135–45, doi:10.1016/j.sbi.2015.08.008.","short":"J.A. Letts, L.A. Sazanov, Current Opinion in Structural Biology 33 (2015) 135–145.","ieee":"J. A. Letts and L. A. Sazanov, “Gaining mass: The structure of respiratory complex I-from bacterial towards mitochondrial versions,” Current Opinion in Structural Biology, vol. 33, no. 8. Elsevier, pp. 135–145, 2015.","apa":"Letts, J. A., & Sazanov, L. A. (2015). Gaining mass: The structure of respiratory complex I-from bacterial towards mitochondrial versions. Current Opinion in Structural Biology. Elsevier. https://doi.org/10.1016/j.sbi.2015.08.008","ama":"Letts JA, Sazanov LA. Gaining mass: The structure of respiratory complex I-from bacterial towards mitochondrial versions. Current Opinion in Structural Biology. 2015;33(8):135-145. doi:10.1016/j.sbi.2015.08.008"},"date_updated":"2021-01-12T06:52:30Z","department":[{"_id":"LeSa"}],"title":"Gaining mass: The structure of respiratory complex I-from bacterial towards mitochondrial versions","author":[{"full_name":"Letts, Jame A","orcid":"0000-0002-9864-3586","last_name":"Letts","id":"322DA418-F248-11E8-B48F-1D18A9856A87","first_name":"Jame A"},{"orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","last_name":"Sazanov","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","first_name":"Leonid A"}],"publist_id":"5465"}]