[{"OA_type":"gold","acknowledgement":"We thank C. Cuveillier, J. Delaroche, T. Ferraro, and A. Zanchi for help with TIRF experiments, electron microscopy preparation, data analysis, and cell cultures, respectively; A. Antkowiak, C. Bosc, C. Fassier, A. Fourest-Lieuvin, and V. Brandt for helpful discussions. We acknowledge the contribution of the Photonic Imaging Center of Grenoble Institute Neuroscience which is part of the ISdV core facility and certified by the IBiSA label and ICM.Quant (RRID:SCR_026393) core facility of the Paris Brain Institute (ICM); the AniRA lentivector production facility from the CELPHEDIA Infrastructure and SFR Biosciences (UAR3444/CNRS, US8/Inserm, ENS de Lyon, UCBL); the Scientific Service Units (SSUs) of ISTA through resources provided by Scientific Computing (SciComp, A. Schloegl and S. Elefante); and the Electron Microscopy Facility (EMF, V.V. Hodirnau). The software programs used for the processing were supported by SBGrid (www.sbgrid.org). This work was supported by the Agence Nationale pour la Recherche (AXYON: ANR-18-CE16-0009-01, S.H.), Austrian Science Fund (FWF) grants (P33367, F.K.M.S.; E435, J.M.H.), ChanZuckerberg Initiative (CZI) grant (DAF2021-234754, F.K.M.S.), Hereditary Disease Foundation Research Grant (HDF 990846, M.C.), European Union (ERC: ActinID 101076260, F.K.M.S.), Fondation pour la Recherche Médicale (FRM: équipe labellisée DEQ202203014675, S.H.; PhD fellowship, FDT202001010865, R.C.), Korea Health Industry Development Institute (KHIDI) (Korea-Switzerland global research support grant: RS-2023-00266300, J.-J.S.), National Research Foundation (NRF) of Korea (Korea-Austria collaborative grant NRF-2019K1A3A1A181160, J.-J.S. and F.K.M.S.; NRF-2020R1A2B5B03001517 and RS-2024-00333346 and RS-2024-00436173, J.-J.S.; 2021R1C1C1006700, D.K.).","ddc":["570"],"scopus_import":"1","date_published":"2025-09-19T00:00:00Z","abstract":[{"lang":"eng","text":"The Huntingtin protein (HTT), named for its role in Huntington’s disease, has been best understood as a scaffolding protein that promotes vesicle transport by molecular motors along microtubules. Here, we show that HTT also interacts with the actin cytoskeleton, and its loss of function disturbs the morphology and function of the axonal growth cone. We demonstrate that HTT organizes F-actin into bundles. Cryo–electron tomography (cryo-ET) and subtomogram averaging (STA) structural analyses reveal that HTT’s N-terminal HEAT and Bridge domains wrap around F-actin, while the C-terminal HEAT domain is displaced; furthermore, HTT dimerizes via the N-HEAT domain to bridge parallel actin filaments separated by ~20 nanometers. Our study provides the structural basis for understanding how HTT interacts with and organizes the actin cytoskeleton."}],"status":"public","file":[{"file_name":"2025_ScienceAdvance_Carpentier.pdf","date_updated":"2025-09-23T07:57:51Z","checksum":"4e2407bdabf8d53f399eb8a20d86218e","success":1,"file_size":3599137,"relation":"main_file","file_id":"20372","creator":"dernst","date_created":"2025-09-23T07:57:51Z","access_level":"open_access","content_type":"application/pdf"}],"isi":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"project":[{"_id":"9B954C5C-BA93-11EA-9121-9846C619BF3A","grant_number":"P33367","name":"Structure and isoform diversity of the Arp2/3 complex"},{"name":"In Situ Actin Structures via Hybrid Cryo-electron Microscopy","grant_number":"E435","_id":"7bd318a1-9f16-11ee-852c-cc9217763180"},{"_id":"62909c6f-2b32-11ec-9570-e1476aab5308","grant_number":"CZI01","name":"CryoMinflux-guided in-situ molecular census and structure determination"},{"name":"A molecular atlas of Actin filament IDentities in the cell motility machinery","grant_number":"101076260","_id":"bd980d18-d553-11ed-ba76-ceaa645c97eb"}],"article_type":"original","publication_status":"published","author":[{"last_name":"Carpentier","first_name":"Rémi","full_name":"Carpentier, Rémi"},{"full_name":"Kim, Jaesung","first_name":"Jaesung","last_name":"Kim"},{"first_name":"Mariacristina","full_name":"Capizzi, Mariacristina","last_name":"Capizzi"},{"last_name":"Kim","full_name":"Kim, Hyeongju","first_name":"Hyeongju"},{"orcid":"0000-0001-7149-769X","last_name":"Fäßler","full_name":"Fäßler, Florian","id":"404F5528-F248-11E8-B48F-1D18A9856A87","first_name":"Florian"},{"last_name":"Hansen","orcid":"0000-0001-7967-2085","first_name":"Jesse","full_name":"Hansen, Jesse","id":"1063c618-6f9b-11ec-9123-f912fccded63"},{"first_name":"Min Jeong","full_name":"Kim, Min Jeong","last_name":"Kim"},{"last_name":"Denarier","full_name":"Denarier, Eric","first_name":"Eric"},{"last_name":"Blot","full_name":"Blot, Béatrice","first_name":"Béatrice"},{"full_name":"Degennaro, Marine","first_name":"Marine","last_name":"Degennaro"},{"last_name":"Labou","first_name":"Sophia","full_name":"Labou, Sophia"},{"full_name":"Arnal, Isabelle","first_name":"Isabelle","last_name":"Arnal"},{"last_name":"Marcaida","first_name":"Maria J.","full_name":"Marcaida, Maria J."},{"last_name":"Peraro","full_name":"Peraro, Matteo Dal","first_name":"Matteo Dal"},{"first_name":"Doory","full_name":"Kim, Doory","last_name":"Kim"},{"full_name":"Schur, Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","first_name":"Florian KM","last_name":"Schur","orcid":"0000-0003-4790-8078"},{"last_name":"Song","first_name":"Ji-Joon","full_name":"Song, Ji-Joon"},{"full_name":"Humbert, Sandrine","first_name":"Sandrine","last_name":"Humbert"}],"title":"Structure of the Huntingtin F-actin complex reveals its role in cytoskeleton organization","year":"2025","_id":"20370","issue":"38","oa_version":"Published Version","pmid":1,"month":"09","article_processing_charge":"Yes","date_updated":"2026-02-16T11:45:54Z","has_accepted_license":"1","OA_place":"publisher","external_id":{"isi":["001575751700013"],"pmid":["40971423"]},"corr_author":"1","intvolume":"        11","quality_controlled":"1","language":[{"iso":"eng"}],"publication_identifier":{"issn":["2375-2548"]},"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)"},"file_date_updated":"2025-09-23T07:57:51Z","date_created":"2025-09-22T08:00:52Z","article_number":"eadw4124","PlanS_conform":"1","department":[{"_id":"FlSc"}],"publisher":"AAAS","day":"19","doi":"10.1126/sciadv.adw4124","type":"journal_article","DOAJ_listed":"1","citation":{"apa":"Carpentier, R., Kim, J., Capizzi, M., Kim, H., Fäßler, F., Hansen, J., … Humbert, S. (2025). Structure of the Huntingtin F-actin complex reveals its role in cytoskeleton organization. <i>Science Advances</i>. AAAS. <a href=\"https://doi.org/10.1126/sciadv.adw4124\">https://doi.org/10.1126/sciadv.adw4124</a>","mla":"Carpentier, Rémi, et al. “Structure of the Huntingtin F-Actin Complex Reveals Its Role in Cytoskeleton Organization.” <i>Science Advances</i>, vol. 11, no. 38, eadw4124, AAAS, 2025, doi:<a href=\"https://doi.org/10.1126/sciadv.adw4124\">10.1126/sciadv.adw4124</a>.","ista":"Carpentier R, Kim J, Capizzi M, Kim H, Fäßler F, Hansen J, Kim MJ, Denarier E, Blot B, Degennaro M, Labou S, Arnal I, Marcaida MJ, Peraro MD, Kim D, Schur FK, Song J-J, Humbert S. 2025. Structure of the Huntingtin F-actin complex reveals its role in cytoskeleton organization. Science Advances. 11(38), eadw4124.","ieee":"R. Carpentier <i>et al.</i>, “Structure of the Huntingtin F-actin complex reveals its role in cytoskeleton organization,” <i>Science Advances</i>, vol. 11, no. 38. AAAS, 2025.","short":"R. Carpentier, J. Kim, M. Capizzi, H. Kim, F. Fäßler, J. Hansen, M.J. Kim, E. Denarier, B. Blot, M. Degennaro, S. Labou, I. Arnal, M.J. Marcaida, M.D. Peraro, D. Kim, F.K. Schur, J.-J. Song, S. Humbert, Science Advances 11 (2025).","chicago":"Carpentier, Rémi, Jaesung Kim, Mariacristina Capizzi, Hyeongju Kim, Florian Fäßler, Jesse Hansen, Min Jeong Kim, et al. “Structure of the Huntingtin F-Actin Complex Reveals Its Role in Cytoskeleton Organization.” <i>Science Advances</i>. AAAS, 2025. <a href=\"https://doi.org/10.1126/sciadv.adw4124\">https://doi.org/10.1126/sciadv.adw4124</a>.","ama":"Carpentier R, Kim J, Capizzi M, et al. Structure of the Huntingtin F-actin complex reveals its role in cytoskeleton organization. <i>Science Advances</i>. 2025;11(38). doi:<a href=\"https://doi.org/10.1126/sciadv.adw4124\">10.1126/sciadv.adw4124</a>"},"volume":11,"publication":"Science Advances"},{"abstract":[{"text":"The extracellular matrix (ECM) serves as a scaffold for cells and plays an essential role in regulating numerous cellular processes, including cell migration and proliferation. Due to limitations in specimen preparation for conventional room-temperature electron microscopy, we lack structural knowledge on how ECM components are secreted, remodeled, and interact with surrounding cells. We have developed a 3D-ECM platform compatible with sample thinning by cryo-focused ion beam milling, the lift-out extraction procedure, and cryo-electron tomography. Our workflow implements cell-derived matrices (CDMs) grown on EM grids, resulting in a versatile tool closely mimicking ECM environments. This allows us to visualize ECM for the first time in its hydrated, native context. Our data reveal an intricate network of extracellular fibers, their positioning relative to matrix-secreting cells, and previously unresolved structural entities. Our workflow and results add to the structural atlas of the ECM, providing novel insights into its secretion and assembly.","lang":"eng"}],"scopus_import":"1","date_published":"2024-03-20T00:00:00Z","status":"public","ddc":["570"],"acknowledgement":"Open Access funding provided by IST Austria. We thank Armel Nicolas and his team at the ISTA proteomics facility, Alois Schloegl, Stefano Elefante, and colleagues at the ISTA Scientific Computing facility, Tommaso Constanzo and Ludek Lovicar at the Electron Microsocpy Facility (EMF), and Thomas Menner at the Miba Machine shop for their support. We also thank Wanda Kukulski (University of Bern) as well as Darío Porley, Andreas Thader, and other members of the Schur group for helpful discussions. Matt Swulius and Jessica Heebner provided great support in using Dragonfly. We thank Dorotea Fracciolla (Art & Science) for support in figure illustration.\r\n\r\nThis research was supported by the Scientific Service Units of ISTA through resources provided by Scientific Computing, the Lab Support Facility, and the Electron Microscopy Facility. We acknowledge funding support from the following sources: Austrian Science Fund (FWF) grant P33367 (to F.K.M. Schur), the Federation of European Biochemical Societies (to F.K.M. Schur), Niederösterreich (NÖ) Fonds (to B. Zens), FWF grant E435 (to J.M. Hansen), European Research Council under the European Union’s Horizon 2020 research (grant agreement No. 724373) (to M. Sixt), and Jenny and Antti Wihuri Foundation (to J. Alanko). This publication has been made possible in part by CZI grant DAF2021-234754 and grant DOI https://doi.org/10.37921/812628ebpcwg from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation (to F.K.M. Schur).","article_type":"original","publication_status":"published","project":[{"_id":"9B954C5C-BA93-11EA-9121-9846C619BF3A","grant_number":"P33367","name":"Structure and isoform diversity of the Arp2/3 complex"},{"_id":"7bd318a1-9f16-11ee-852c-cc9217763180","grant_number":"E435","name":"In Situ Actin Structures via Hybrid Cryo-electron Microscopy"},{"call_identifier":"H2020","name":"Cellular Navigation Along Spatial Gradients","_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373"},{"name":"NÖ-Fonds Preis für die Jungforscherin des Jahres am IST Austria","_id":"059B463C-7A3F-11EA-A408-12923DDC885E"},{"name":"Spatiotemporal regulation of chemokine-induced signalling in leukocyte chemotaxis","_id":"2615199A-B435-11E9-9278-68D0E5697425","grant_number":"21317"},{"grant_number":"CZI01","_id":"62909c6f-2b32-11ec-9570-e1476aab5308","name":"CryoMinflux-guided in-situ visual proteomics and structure determination"}],"author":[{"last_name":"Zens","orcid":"0000-0002-9561-1239","first_name":"Bettina","id":"45FD126C-F248-11E8-B48F-1D18A9856A87","full_name":"Zens, Bettina"},{"orcid":"0000-0001-7149-769X","last_name":"Fäßler","id":"404F5528-F248-11E8-B48F-1D18A9856A87","full_name":"Fäßler, Florian","first_name":"Florian"},{"id":"1063c618-6f9b-11ec-9123-f912fccded63","full_name":"Hansen, Jesse","first_name":"Jesse","orcid":"0000-0001-7967-2085","last_name":"Hansen"},{"full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert","last_name":"Hauschild","orcid":"0000-0001-9843-3522"},{"last_name":"Datler","orcid":"0000-0002-3616-8580","first_name":"Julia","id":"3B12E2E6-F248-11E8-B48F-1D18A9856A87","full_name":"Datler, Julia"},{"orcid":"0000-0003-3904-947X","last_name":"Hodirnau","full_name":"Hodirnau, Victor-Valentin","id":"3661B498-F248-11E8-B48F-1D18A9856A87","first_name":"Victor-Valentin"},{"first_name":"Vanessa","id":"39C5A68A-F248-11E8-B48F-1D18A9856A87","full_name":"Zheden, Vanessa","last_name":"Zheden","orcid":"0000-0002-9438-4783"},{"orcid":"0000-0002-7698-3061","last_name":"Alanko","first_name":"Jonna H","id":"2CC12E8C-F248-11E8-B48F-1D18A9856A87","full_name":"Alanko, Jonna H"},{"first_name":"Michael K","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","orcid":"0000-0002-6620-9179"},{"orcid":"0000-0003-4790-8078","last_name":"Schur","first_name":"Florian KM","full_name":"Schur, Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87"}],"isi":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","file":[{"file_id":"15188","file_size":11907016,"relation":"main_file","content_type":"application/pdf","access_level":"open_access","creator":"dernst","date_created":"2024-03-25T12:52:04Z","date_updated":"2024-03-25T12:52:04Z","file_name":"2024_JCB_Zens.pdf","success":1,"checksum":"90d1984a93660735e506c2a304bc3f73"}],"oa":1,"_id":"15146","issue":"6","year":"2024","oa_version":"Published Version","title":"Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural landscape of extracellular matrix","article_processing_charge":"Yes (via OA deal)","pmid":1,"month":"03","quality_controlled":"1","language":[{"iso":"eng"}],"intvolume":"       223","publication_identifier":{"eissn":["1540-8140"],"issn":["0021-9525"]},"has_accepted_license":"1","date_updated":"2025-09-04T13:17:16Z","corr_author":"1","external_id":{"pmid":["38506714"],"isi":["001264190100001"]},"file_date_updated":"2024-03-25T12:52:04Z","date_created":"2024-03-21T06:45:51Z","department":[{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"Bio"},{"_id":"EM-Fac"}],"article_number":"e202309125","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)"},"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"ScienComp"},{"_id":"EM-Fac"},{"_id":"M-Shop"}],"citation":{"mla":"Zens, Bettina, et al. “Lift-out Cryo-FIBSEM and Cryo-ET Reveal the Ultrastructural Landscape of Extracellular Matrix.” <i>Journal of Cell Biology</i>, vol. 223, no. 6, e202309125, Rockefeller University Press, 2024, doi:<a href=\"https://doi.org/10.1083/jcb.202309125\">10.1083/jcb.202309125</a>.","ista":"Zens B, Fäßler F, Hansen J, Hauschild R, Datler J, Hodirnau V-V, Zheden V, Alanko JH, Sixt MK, Schur FK. 2024. Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural landscape of extracellular matrix. Journal of Cell Biology. 223(6), e202309125.","apa":"Zens, B., Fäßler, F., Hansen, J., Hauschild, R., Datler, J., Hodirnau, V.-V., … Schur, F. K. (2024). Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural landscape of extracellular matrix. <i>Journal of Cell Biology</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1083/jcb.202309125\">https://doi.org/10.1083/jcb.202309125</a>","ieee":"B. Zens <i>et al.</i>, “Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural landscape of extracellular matrix,” <i>Journal of Cell Biology</i>, vol. 223, no. 6. Rockefeller University Press, 2024.","short":"B. Zens, F. Fäßler, J. Hansen, R. Hauschild, J. Datler, V.-V. Hodirnau, V. Zheden, J.H. Alanko, M.K. Sixt, F.K. Schur, Journal of Cell Biology 223 (2024).","chicago":"Zens, Bettina, Florian Fäßler, Jesse Hansen, Robert Hauschild, Julia Datler, Victor-Valentin Hodirnau, Vanessa Zheden, Jonna H Alanko, Michael K Sixt, and Florian KM Schur. “Lift-out Cryo-FIBSEM and Cryo-ET Reveal the Ultrastructural Landscape of Extracellular Matrix.” <i>Journal of Cell Biology</i>. Rockefeller University Press, 2024. <a href=\"https://doi.org/10.1083/jcb.202309125\">https://doi.org/10.1083/jcb.202309125</a>.","ama":"Zens B, Fäßler F, Hansen J, et al. Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural landscape of extracellular matrix. <i>Journal of Cell Biology</i>. 2024;223(6). doi:<a href=\"https://doi.org/10.1083/jcb.202309125\">10.1083/jcb.202309125</a>"},"volume":223,"day":"20","publisher":"Rockefeller University Press","doi":"10.1083/jcb.202309125","ec_funded":1,"type":"journal_article","publication":"Journal of Cell Biology"},{"publication":"Nature Structural & Molecular Biology","volume":31,"citation":{"ama":"Datler J, Hansen J, Thader A, et al. Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores. <i>Nature Structural &#38; Molecular Biology</i>. 2024;31:1114-1123. doi:<a href=\"https://doi.org/10.1038/s41594-023-01201-6\">10.1038/s41594-023-01201-6</a>","chicago":"Datler, Julia, Jesse Hansen, Andreas Thader, Alois Schlögl, Lukas W Bauer, Victor-Valentin Hodirnau, and Florian KM Schur. “Multi-Modal Cryo-EM Reveals Trimers of Protein A10 to Form the Palisade Layer in Poxvirus Cores.” <i>Nature Structural &#38; Molecular Biology</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41594-023-01201-6\">https://doi.org/10.1038/s41594-023-01201-6</a>.","short":"J. Datler, J. Hansen, A. Thader, A. Schlögl, L.W. Bauer, V.-V. Hodirnau, F.K. Schur, Nature Structural &#38; Molecular Biology 31 (2024) 1114–1123.","ieee":"J. Datler <i>et al.</i>, “Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores,” <i>Nature Structural &#38; Molecular Biology</i>, vol. 31. Springer Nature, pp. 1114–1123, 2024.","ista":"Datler J, Hansen J, Thader A, Schlögl A, Bauer LW, Hodirnau V-V, Schur FK. 2024. Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores. Nature Structural &#38; Molecular Biology. 31, 1114–1123.","apa":"Datler, J., Hansen, J., Thader, A., Schlögl, A., Bauer, L. W., Hodirnau, V.-V., &#38; Schur, F. K. (2024). Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores. <i>Nature Structural &#38; Molecular Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41594-023-01201-6\">https://doi.org/10.1038/s41594-023-01201-6</a>","mla":"Datler, Julia, et al. “Multi-Modal Cryo-EM Reveals Trimers of Protein A10 to Form the Palisade Layer in Poxvirus Cores.” <i>Nature Structural &#38; Molecular Biology</i>, vol. 31, Springer Nature, 2024, pp. 1114–23, doi:<a href=\"https://doi.org/10.1038/s41594-023-01201-6\">10.1038/s41594-023-01201-6</a>."},"type":"journal_article","related_material":{"link":[{"url":"https://ista.ac.at/en/news/down-to-the-core-of-poxviruses/","relation":"press_release","description":"News on ISTA Website"}],"record":[{"relation":"dissertation_contains","id":"18766","status":"public"}]},"publisher":"Springer Nature","day":"01","doi":"10.1038/s41594-023-01201-6","page":"1114-1123","department":[{"_id":"FlSc"},{"_id":"ScienComp"},{"_id":"EM-Fac"}],"date_created":"2024-02-12T09:59:45Z","file_date_updated":"2024-07-22T11:27:22Z","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"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)"},"publication_identifier":{"eissn":["1545-9985"],"issn":["1545-9993"]},"quality_controlled":"1","language":[{"iso":"eng"}],"intvolume":"        31","corr_author":"1","external_id":{"isi":["001158144600002"],"pmid":["38316877"]},"has_accepted_license":"1","OA_place":"publisher","date_updated":"2026-04-07T12:59:44Z","article_processing_charge":"Yes (in subscription journal)","month":"07","pmid":1,"oa_version":"Published Version","_id":"14979","year":"2024","keyword":["Molecular Biology","Structural Biology"],"APC_amount":"11700 EUR","title":"Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores","author":[{"orcid":"0000-0002-3616-8580","last_name":"Datler","first_name":"Julia","id":"3B12E2E6-F248-11E8-B48F-1D18A9856A87","full_name":"Datler, Julia"},{"id":"1063c618-6f9b-11ec-9123-f912fccded63","full_name":"Hansen, Jesse","first_name":"Jesse","orcid":"0000-0001-7967-2085","last_name":"Hansen"},{"last_name":"Thader","full_name":"Thader, Andreas","id":"3A18A7B8-F248-11E8-B48F-1D18A9856A87","first_name":"Andreas"},{"orcid":"0000-0002-5621-8100","last_name":"Schlögl","full_name":"Schlögl, Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","first_name":"Alois"},{"first_name":"Lukas W","id":"0c894dcf-897b-11ed-a09c-8186353224b0","full_name":"Bauer, Lukas W","last_name":"Bauer"},{"first_name":"Victor-Valentin","full_name":"Hodirnau, Victor-Valentin","id":"3661B498-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3904-947X","last_name":"Hodirnau"},{"last_name":"Schur","orcid":"0000-0003-4790-8078","first_name":"Florian KM","full_name":"Schur, Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87"}],"article_type":"original","publication_status":"published","project":[{"grant_number":"P31445","_id":"26736D6A-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Structural conservation and diversity in retroviral capsid"}],"oa":1,"isi":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","file":[{"file_id":"17307","relation":"main_file","file_size":17485494,"content_type":"application/pdf","access_level":"open_access","date_created":"2024-07-22T11:27:22Z","creator":"dernst","date_updated":"2024-07-22T11:27:22Z","file_name":"2024_NatureStrucBio_Datler.pdf","success":1,"checksum":"bda7bf65d81455480efaed8ca293b0db"}],"status":"public","abstract":[{"lang":"eng","text":"Poxviruses are among the largest double-stranded DNA viruses, with members such as variola virus, monkeypox virus and the vaccination strain vaccinia virus (VACV). Knowledge about the structural proteins that form the viral core has remained sparse. While major core proteins have been annotated via indirect experimental evidence, their structures have remained elusive and they could not be assigned to individual core features. Hence, which proteins constitute which layers of the core, such as the palisade layer and the inner core wall, has remained enigmatic. Here we show, using a multi-modal cryo-electron microscopy (cryo-EM) approach in combination with AlphaFold molecular modeling, that trimers formed by the cleavage product of VACV protein A10 are the key component of the palisade layer. This allows us to place previously obtained descriptions of protein interactions within the core wall into perspective and to provide a detailed model of poxvirus core architecture. Importantly, we show that interactions within A10 trimers are likely generalizable over members of orthopox- and parapoxviruses."}],"scopus_import":"1","date_published":"2024-07-01T00:00:00Z","ddc":["570"],"acknowledgement":"We thank A. Bergthaler (Research Center for Molecular Medicine of the Austrian Academy of Sciences) for providing VACV WR. We thank A. Nicholas and his team at the ISTA proteomics facility, and S. Elefante at the ISTA Scientific Computing facility for their support. We also thank F. Fäßler, D. Porley, T. Muthspiel and other members of the Schur group for support and helpful discussions. We also thank D. Castaño-Díez for support with Dynamo. We thank D. Farrell for his help optimizing the Rosetta protocol to refine the atomic model into the cryo-EM map with symmetry.\r\n\r\nF.K.M.S. acknowledges support from ISTA and EMBO. F.K.M.S. also received support from the Austrian Science Fund (FWF) grant P31445. This publication has been made possible in part by CZI grant DAF2021-234754 and grant https://doi.org/10.37921/812628ebpcwg from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation (funder https://doi.org/10.13039/100014989) awarded to F.K.M.S.\r\n\r\nThis research was also supported by the Scientific Service Units (SSUs) of ISTA through resources provided by Scientific Computing (SciComp), the Life Science Facility (LSF), and the Electron Microscopy Facility (EMF). We also acknowledge the use of COSMIC45 and Colabfold46.","OA_type":"hybrid"}]