[{"article_number":"e70630","citation":{"ieee":"J. Schneider, U. Guillerm, C. Simoes Pereira, and P. Schanda, “Dynamic disorder is crucial for mitochondrial protein import,” <i>Protein Science</i>, vol. 35, no. 6. Wiley, 2026.","apa":"Schneider, J., Guillerm, U., Simoes Pereira, C., &#38; Schanda, P. (2026). Dynamic disorder is crucial for mitochondrial protein import. <i>Protein Science</i>. Wiley. <a href=\"https://doi.org/10.1002/pro.70630\">https://doi.org/10.1002/pro.70630</a>","chicago":"Schneider, Jakob, Undina Guillerm, Caroline Simoes Pereira, and Paul Schanda. “Dynamic Disorder Is Crucial for Mitochondrial Protein Import.” <i>Protein Science</i>. Wiley, 2026. <a href=\"https://doi.org/10.1002/pro.70630\">https://doi.org/10.1002/pro.70630</a>.","ama":"Schneider J, Guillerm U, Simoes Pereira C, Schanda P. Dynamic disorder is crucial for mitochondrial protein import. <i>Protein Science</i>. 2026;35(6). doi:<a href=\"https://doi.org/10.1002/pro.70630\">10.1002/pro.70630</a>","ista":"Schneider J, Guillerm U, Simoes Pereira C, Schanda P. 2026. Dynamic disorder is crucial for mitochondrial protein import. Protein Science. 35(6), e70630.","short":"J. Schneider, U. Guillerm, C. Simoes Pereira, P. Schanda, Protein Science 35 (2026).","mla":"Schneider, Jakob, et al. “Dynamic Disorder Is Crucial for Mitochondrial Protein Import.” <i>Protein Science</i>, vol. 35, no. 6, e70630, Wiley, 2026, doi:<a href=\"https://doi.org/10.1002/pro.70630\">10.1002/pro.70630</a>."},"language":[{"iso":"eng"}],"date_created":"2026-05-31T22:02:12Z","oa_version":"Published Version","publication":"Protein Science","OA_type":"hybrid","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","external_id":{"pmid":["42159315"]},"publication_status":"published","license":"https://creativecommons.org/licenses/by/4.0/","ddc":["572"],"publisher":"Wiley","publication_identifier":{"eissn":["1469-896X"],"issn":["0961-8368"]},"acknowledgement":"We gratefully acknowledge research funding by the Austrian Science Fund (FWF), projects 10.55776/PAT1647625 and 10.55776/I6223. We thank Prof. Long Li (Peking University) for providing structural models and EM density for the TOM and TIM23 complexes, used to generate part of Figure 3. Open Access funding provided by Institute of Science and Technology Austria.","volume":35,"date_updated":"2026-06-02T07:26:34Z","OA_place":"publisher","fulldoi":"https://doi.org/10.1002/pro.70630","article_processing_charge":"Yes (via OA deal)","file_date_updated":"2026-06-02T07:23:12Z","issue":"6","month":"06","author":[{"full_name":"Schneider, Jakob","id":"64368429-eb97-11eb-a6c2-c980b1f44415","last_name":"Schneider","first_name":"Jakob"},{"id":"bb74f472-ae54-11eb-9835-bc9c22fb1183","last_name":"Guillerm","full_name":"Guillerm, Undina","first_name":"Undina"},{"first_name":"Caroline","id":"87266c4a-96d2-11ef-be2c-fe5633233ec3","last_name":"Simoes Pereira","full_name":"Simoes Pereira, Caroline"},{"orcid":"0000-0002-9350-7606","first_name":"Paul","full_name":"Schanda, Paul","id":"7B541462-FAF6-11E9-A490-E8DFE5697425","last_name":"Schanda"}],"day":"01","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":"        35","year":"2026","oa":1,"has_accepted_license":"1","department":[{"_id":"GradSch"},{"_id":"PaSc"}],"project":[{"grant_number":"I06223","_id":"bdb9578d-d553-11ed-ba76-ed5d39fce6f0","name":"Structure and mechanism of the mitochondrial MIM insertase"}],"corr_author":"1","file":[{"checksum":"e0163459a7238fdcc3fc5e17bedcce9a","access_level":"open_access","file_size":3897305,"date_updated":"2026-06-02T07:23:12Z","content_type":"application/pdf","creator":"dernst","file_id":"21937","relation":"main_file","date_created":"2026-06-02T07:23:12Z","file_name":"2026_ProteinScience_Schneider.pdf","success":1}],"date_published":"2026-06-01T00:00:00Z","quality_controlled":"1","pmid":1,"title":"Dynamic disorder is crucial for mitochondrial protein import","doi":"10.1002/pro.70630","article_type":"original","PlanS_conform":"1","scopus_import":"1","_id":"21929","status":"public","abstract":[{"lang":"eng","text":"The import of proteins into mitochondria poses fundamental mechanistic challenges: aggregation-prone precursor proteins must be maintained in aqueous compartments and threaded through narrow pores without becoming stuck or mislocalized. Recent evidence from mitochondrial protein import studies and other chaperone systems underscores the critical role of dynamics in balancing sufficiently tight binding, promiscuity, specificity, and release. Dynamic binding of client precursor proteins to import machinery components arises naturally from the avidity of their interactions. Conformational entropy enhances their stability, while the multivalent nature of these interactions ensures that client transfer to downstream insertases occurs without a substantial energy barrier. Here, we discuss this emerging paradigm of dynamic protein handling, using examples where dynamic structures have been resolved and highlight outstanding questions."}]},{"scopus_import":"1","article_type":"original","PlanS_conform":"1","status":"public","_id":"21777","abstract":[{"lang":"eng","text":"The advantageous characteristics attributed to the 19F nucleus have made it a popular target for nuclear magnetic resonance (NMR) once again in recent years. Aside from solution NMR, an increasing number of studies have been conducted applying solid-state magic-angle spinning (MAS) NMR to fluorine-labelled samples. Here, the high chemical shift anisotropy and strong dipolar couplings can be utilised to get structural insights into proteins and measure long distances. Despite increasing popularity and promising benefits, the sensitivity of biomolecular 19F MAS NMR often suffers from slow longitudinal T1 relaxation and therefore long recycle delays. In this work, we expand paramagnetic doping, an approach commonly used to reduce proton T1 relaxation times, to 19F-labelled biological samples. We study the effect of Gd(DTPA) and Gd(DTPA-BMA) on 19F T1 and T2, and 13C T1 and T2 relaxation in a [5-19F13C]-tryptophan-labelled protein via 19F-detected MAS NMR experiments. The observed paramagnetic relaxation enhancement substantially reduces measurement times of 19F MAS NMR experiments without compromising resolution. Additionally, we report the chemical shift assignments of all four fluorotryptophan signals in the 12×39 kDa-large protein TET2 using a mutagenesis approach."}],"title":"Accelerated 19F biomolecular magic-angle spinning NMR with paramagnetic dopants","pmid":1,"doi":"10.5194/mr-7-29-2026","corr_author":"1","project":[{"_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854","name":"IST Austria Open Access Fund"},{"name":"Exploring protein dynamics by solid-state MAS NMR through specific labeling approaches","_id":"7be609c4-9f16-11ee-852c-85015ce2b9b0","grant_number":"26777"}],"department":[{"_id":"PaSc"},{"_id":"GradSch"}],"quality_controlled":"1","date_published":"2026-04-16T00:00:00Z","oa":1,"has_accepted_license":"1","year":"2026","intvolume":"         7","acknowledged_ssus":[{"_id":"NMR"},{"_id":"LifeSc"}],"month":"04","issue":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"full_name":"Becker, Lea Marie","id":"36336939-eb97-11eb-a6c2-c83f1214ca79","last_name":"Becker","first_name":"Lea Marie","orcid":"0000-0002-6401-5151"},{"full_name":"Toscano, Giorgia","id":"334a5e40-8747-11f0-b671-ba1f5154b4b4","last_name":"Toscano","first_name":"Giorgia"},{"last_name":"Kapitonova","id":"9fb2a840-89e1-11ee-a8b7-cc5c7ba62471","full_name":"Kapitonova, Anna","first_name":"Anna"},{"last_name":"Singh","id":"a3089acd-6806-11ee-bacc-f0c7d500ad20","full_name":"Singh, Rajkumar","first_name":"Rajkumar"},{"first_name":"Undina","full_name":"Guillerm, Undina","last_name":"Guillerm","id":"bb74f472-ae54-11eb-9835-bc9c22fb1183"},{"first_name":"Roman J.","last_name":"Lichtenecker","full_name":"Lichtenecker, Roman J."},{"last_name":"Schanda","id":"7B541462-FAF6-11E9-A490-E8DFE5697425","full_name":"Schanda, Paul","first_name":"Paul","orcid":"0000-0002-9350-7606"}],"page":"29-37","day":"16","OA_place":"publisher","fulldoi":"https://doi.org/10.5194/mr-7-29-2026","article_processing_charge":"Yes","date_updated":"2026-07-20T09:49:12Z","related_material":{"record":[{"relation":"dissertation_contains","id":"22334","status":"public"}]},"acknowledgement":"We thank Ben P. Tatman for insightful discussions. This research was supported by the Scientific Service Units (SSUs) of ISTA through resources provided by the Nuclear Magnetic Resonance Facility and the Lab Support Facility. We thank Prof. Tobias Madl (Medical University Graz) for a sample of Omniscan. Lea M. Becker is the recipient of a DOC fellowship of the Austrian Academy of Sciences at the Institute of Science and Technology Austria (grant no. PR10660EAW01).","volume":7,"publisher":"Copernicus Publications","publication_identifier":{"eissn":["2699-0016"]},"ddc":["540"],"DOAJ_listed":"1","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"publication_status":"published","external_id":{"pmid":["42057802"]},"publication":"Magnetic Resonance","OA_type":"gold","oa_version":"Published Version","main_file_link":[{"open_access":"1","url":"https://doi.org/10.5194/mr-7-29-2026"}],"date_created":"2026-05-03T22:01:36Z","citation":{"mla":"Becker, Lea Marie, et al. “Accelerated 19F Biomolecular Magic-Angle Spinning NMR with Paramagnetic Dopants.” <i>Magnetic Resonance</i>, vol. 7, no. 1, Copernicus Publications, 2026, pp. 29–37, doi:<a href=\"https://doi.org/10.5194/mr-7-29-2026\">10.5194/mr-7-29-2026</a>.","ista":"Becker LM, Toscano G, Kapitonova A, Singh R, Guillerm U, Lichtenecker RJ, Schanda P. 2026. Accelerated 19F biomolecular magic-angle spinning NMR with paramagnetic dopants. Magnetic Resonance. 7(1), 29–37.","short":"L.M. Becker, G. Toscano, A. Kapitonova, R. Singh, U. Guillerm, R.J. Lichtenecker, P. Schanda, Magnetic Resonance 7 (2026) 29–37.","chicago":"Becker, Lea Marie, Giorgia Toscano, Anna Kapitonova, Rajkumar Singh, Undina Guillerm, Roman J. Lichtenecker, and Paul Schanda. “Accelerated 19F Biomolecular Magic-Angle Spinning NMR with Paramagnetic Dopants.” <i>Magnetic Resonance</i>. Copernicus Publications, 2026. <a href=\"https://doi.org/10.5194/mr-7-29-2026\">https://doi.org/10.5194/mr-7-29-2026</a>.","ama":"Becker LM, Toscano G, Kapitonova A, et al. Accelerated 19F biomolecular magic-angle spinning NMR with paramagnetic dopants. <i>Magnetic Resonance</i>. 2026;7(1):29-37. doi:<a href=\"https://doi.org/10.5194/mr-7-29-2026\">10.5194/mr-7-29-2026</a>","ieee":"L. M. Becker <i>et al.</i>, “Accelerated 19F biomolecular magic-angle spinning NMR with paramagnetic dopants,” <i>Magnetic Resonance</i>, vol. 7, no. 1. Copernicus Publications, pp. 29–37, 2026.","apa":"Becker, L. M., Toscano, G., Kapitonova, A., Singh, R., Guillerm, U., Lichtenecker, R. J., &#38; Schanda, P. (2026). Accelerated 19F biomolecular magic-angle spinning NMR with paramagnetic dopants. <i>Magnetic Resonance</i>. Copernicus Publications. <a href=\"https://doi.org/10.5194/mr-7-29-2026\">https://doi.org/10.5194/mr-7-29-2026</a>"},"language":[{"iso":"eng"}]},{"publisher":"Elsevier","publication_identifier":{"issn":["0076-6879"]},"date_updated":"2025-10-22T06:40:54Z","volume":707,"date_created":"2024-10-01T10:58:27Z","citation":{"ama":"Guillerm U, Sučec I, Schanda P. Generation of TIM chaperone substrate complexes. In: <i>Methods in Enzymology</i>. Vol 707. Elsevier; 2024:391-422. doi:<a href=\"https://doi.org/10.1016/bs.mie.2024.07.051\">10.1016/bs.mie.2024.07.051</a>","chicago":"Guillerm, Undina, Iva Sučec, and Paul Schanda. “Generation of TIM Chaperone Substrate Complexes.” In <i>Methods in Enzymology</i>, 707:391–422. Elsevier, 2024. <a href=\"https://doi.org/10.1016/bs.mie.2024.07.051\">https://doi.org/10.1016/bs.mie.2024.07.051</a>.","apa":"Guillerm, U., Sučec, I., &#38; Schanda, P. (2024). Generation of TIM chaperone substrate complexes. In <i>Methods in Enzymology</i> (Vol. 707, pp. 391–422). Elsevier. <a href=\"https://doi.org/10.1016/bs.mie.2024.07.051\">https://doi.org/10.1016/bs.mie.2024.07.051</a>","ieee":"U. Guillerm, I. Sučec, and P. Schanda, “Generation of TIM chaperone substrate complexes,” in <i>Methods in Enzymology</i>, vol. 707, Elsevier, 2024, pp. 391–422.","mla":"Guillerm, Undina, et al. “Generation of TIM Chaperone Substrate Complexes.” <i>Methods in Enzymology</i>, vol. 707, Elsevier, 2024, pp. 391–422, doi:<a href=\"https://doi.org/10.1016/bs.mie.2024.07.051\">10.1016/bs.mie.2024.07.051</a>.","short":"U. Guillerm, I. Sučec, P. Schanda, in:, Methods in Enzymology, Elsevier, 2024, pp. 391–422.","ista":"Guillerm U, Sučec I, Schanda P. 2024.Generation of TIM chaperone substrate complexes. In: Methods in Enzymology. vol. 707, 391–422."},"language":[{"iso":"eng"}],"type":"book_chapter","external_id":{"pmid":["39488384"]},"publication_status":"published","oa_version":"None","OA_type":"closed access","publication":"Methods in Enzymology","department":[{"_id":"PaSc"}],"corr_author":"1","quality_controlled":"1","date_published":"2024-09-13T00:00:00Z","scopus_import":"1","status":"public","_id":"18167","abstract":[{"text":"Holdase chaperones are essential in the mitochondrial membrane-protein biogenesis as they stabilize preproteins and keep them in an import-competent state as they travel through the aqueous cytosol and intermembrane space. The small TIM chaperones of the mitochondrial intermembrane space function within a fine balance of client promiscuity and high affinity binding, while being also able to release their client proteins without significant energy barrier to the downstream insertases/translocases. The tendency of the preproteins to aggregate and the dynamic nature of the preprotein—chaperone complexes makes the preparation of these complexes challenging. Here we present two optimized methods for complex formation of highly hydrophobic precursor proteins and chaperones: a pull-down approach and an in-vitro translation strategy. In the former, attaching the client protein to an affinity resin keeps the individual client protein copies apart from each other and decreases the client self-aggregation probability, thereby favouring complex formation. In the latter approach, a purified chaperone, added to the cell-free protein synthesis, captures the nascent precursor protein. The choice of method will depend on the desired client-chaperone complex amount, or the need for specific labeling scheme.","lang":"eng"}],"title":"Generation of TIM chaperone substrate complexes","pmid":1,"doi":"10.1016/bs.mie.2024.07.051","month":"09","page":"391-422","author":[{"full_name":"Guillerm, Undina","id":"bb74f472-ae54-11eb-9835-bc9c22fb1183","last_name":"Guillerm","first_name":"Undina"},{"last_name":"Sučec","full_name":"Sučec, Iva","first_name":"Iva"},{"orcid":"0000-0002-9350-7606","full_name":"Schanda, Paul","last_name":"Schanda","id":"7B541462-FAF6-11E9-A490-E8DFE5697425","first_name":"Paul"}],"day":"13","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","fulldoi":"https://doi.org/10.1016/bs.mie.2024.07.051","article_processing_charge":"No","year":"2024","intvolume":"       707"},{"date_created":"2023-05-28T22:01:04Z","language":[{"iso":"eng"}],"citation":{"ama":"Degen M, Santos JC, Pluhackova K, et al. Structural basis of NINJ1-mediated plasma membrane rupture in cell death. <i>Nature</i>. 2023;618:1065-1071. doi:<a href=\"https://doi.org/10.1038/s41586-023-05991-z\">10.1038/s41586-023-05991-z</a>","chicago":"Degen, Morris, José Carlos Santos, Kristyna Pluhackova, Gonzalo Cebrero, Saray Ramos, Gytis Jankevicius, Ella Hartenian, et al. “Structural Basis of NINJ1-Mediated Plasma Membrane Rupture in Cell Death.” <i>Nature</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41586-023-05991-z\">https://doi.org/10.1038/s41586-023-05991-z</a>.","apa":"Degen, M., Santos, J. C., Pluhackova, K., Cebrero, G., Ramos, S., Jankevicius, G., … Hiller, S. (2023). Structural basis of NINJ1-mediated plasma membrane rupture in cell death. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-023-05991-z\">https://doi.org/10.1038/s41586-023-05991-z</a>","ieee":"M. Degen <i>et al.</i>, “Structural basis of NINJ1-mediated plasma membrane rupture in cell death,” <i>Nature</i>, vol. 618. Springer Nature, pp. 1065–1071, 2023.","mla":"Degen, Morris, et al. “Structural Basis of NINJ1-Mediated Plasma Membrane Rupture in Cell Death.” <i>Nature</i>, vol. 618, Springer Nature, 2023, pp. 1065–71, doi:<a href=\"https://doi.org/10.1038/s41586-023-05991-z\">10.1038/s41586-023-05991-z</a>.","short":"M. Degen, J.C. Santos, K. Pluhackova, G. Cebrero, S. Ramos, G. Jankevicius, E. Hartenian, U. Guillerm, S.A. Mari, B. Kohl, D.J. Müller, P. Schanda, T. Maier, C. Perez, C. Sieben, P. Broz, S. Hiller, Nature 618 (2023) 1065–1071.","ista":"Degen M, Santos JC, Pluhackova K, Cebrero G, Ramos S, Jankevicius G, Hartenian E, Guillerm U, Mari SA, Kohl B, Müller DJ, Schanda P, Maier T, Perez C, Sieben C, Broz P, Hiller S. 2023. Structural basis of NINJ1-mediated plasma membrane rupture in cell death. Nature. 618, 1065–1071."},"publication_status":"published","external_id":{"isi":["000991386800011"],"pmid":["37198476"]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","oa_version":"Published Version","publication":"Nature","publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"publisher":"Springer Nature","ddc":["570"],"date_updated":"2025-04-23T08:57:12Z","volume":618,"acknowledgement":"This work was supported by the Deutsche Forschungsgemeinschaft under Germany’s Excellence Strategy EXC 2075–390740016 and the Stuttgart Center for Simulation Science (SC SimTech) to K.P., by ERC-CoG 770988 (InflamCellDeath) and SNF Project funding (310030B_198005, 310030B_192523) to P.B., by the Swiss Nanoscience Institute and the Swiss National Science Foundation via the NCCR AntiResist (180541) to S.H. and the NCCR Molecular Systems Engineering (51NF40-205608) to D.J.M., by the Helmholtz Young Investigator Program of the Helmholtz Association to C.S., by the SNF Professorship funding (PP00P3_198903) to C.P., EMBO postdoctoral fellowship ALTF 27-2022 to E.H. and by the Scientific Service Units of IST Austria through resources provided by the NMR and Life Science Facilities to P.S. Molecular dynamics simulations were performed on the HoreKa supercomputer funded by the Ministry of Science, Research and the Arts Baden-Württemberg and by the Federal Ministry of Education and Research. The authors thank the BioEM Lab of the Biozentrum, University of Basel for support; V. Mack, K. Shkarina and J. Fricke for technical support; D. Ricklin and S. Vogt for peptide synthesis; P. Pelczar for support with animals; S.-J. Marrink and P. Telles de Souza for supply with Martini3 parameters and scripts; and P. Radler und M. Loose for help with QCM. Fig. 4g and Extended Data Fig. 1a were in part created with BioRender.com.\r\nOpen access funding provided by University of Basel.","page":"1065-1071","day":"29","author":[{"first_name":"Morris","full_name":"Degen, Morris","last_name":"Degen"},{"first_name":"José Carlos","full_name":"Santos, José Carlos","last_name":"Santos"},{"last_name":"Pluhackova","full_name":"Pluhackova, Kristyna","first_name":"Kristyna"},{"first_name":"Gonzalo","full_name":"Cebrero, Gonzalo","last_name":"Cebrero"},{"last_name":"Ramos","full_name":"Ramos, Saray","first_name":"Saray"},{"last_name":"Jankevicius","full_name":"Jankevicius, Gytis","first_name":"Gytis"},{"last_name":"Hartenian","full_name":"Hartenian, Ella","first_name":"Ella"},{"full_name":"Guillerm, Undina","id":"bb74f472-ae54-11eb-9835-bc9c22fb1183","last_name":"Guillerm","first_name":"Undina"},{"full_name":"Mari, Stefania A.","last_name":"Mari","first_name":"Stefania A."},{"full_name":"Kohl, Bastian","last_name":"Kohl","first_name":"Bastian"},{"full_name":"Müller, Daniel J.","last_name":"Müller","first_name":"Daniel J."},{"orcid":"0000-0002-9350-7606","first_name":"Paul","full_name":"Schanda, Paul","last_name":"Schanda","id":"7B541462-FAF6-11E9-A490-E8DFE5697425"},{"first_name":"Timm","full_name":"Maier, Timm","last_name":"Maier"},{"full_name":"Perez, Camilo","last_name":"Perez","first_name":"Camilo"},{"last_name":"Sieben","full_name":"Sieben, Christian","first_name":"Christian"},{"first_name":"Petr","full_name":"Broz, Petr","last_name":"Broz"},{"full_name":"Hiller, Sebastian","last_name":"Hiller","first_name":"Sebastian"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"06","article_processing_charge":"Yes (via OA deal)","file_date_updated":"2023-11-14T11:48:18Z","isi":1,"fulldoi":"https://doi.org/10.1038/s41586-023-05991-z","year":"2023","acknowledged_ssus":[{"_id":"NMR"},{"_id":"LifeSc"}],"intvolume":"       618","date_published":"2023-06-29T00:00:00Z","quality_controlled":"1","file":[{"file_id":"14533","creator":"dernst","content_type":"application/pdf","date_updated":"2023-11-14T11:48:18Z","access_level":"open_access","file_size":12292188,"checksum":"0fab69252453bff1de7f0e2eceb76d34","success":1,"file_name":"2023_Nature_Degen.pdf","date_created":"2023-11-14T11:48:18Z","relation":"main_file"}],"department":[{"_id":"PaSc"}],"has_accepted_license":"1","oa":1,"abstract":[{"lang":"eng","text":"Eukaryotic cells can undergo different forms of programmed cell death, many of which culminate in plasma membrane rupture as the defining terminal event1,2,3,4,5,6,7. Plasma membrane rupture was long thought to be driven by osmotic pressure, but it has recently been shown to be in many cases an active process, mediated by the protein ninjurin-18 (NINJ1). Here we resolve the structure of NINJ1 and the mechanism by which it ruptures membranes. Super-resolution microscopy reveals that NINJ1 clusters into structurally diverse assemblies in the membranes of dying cells, in particular large, filamentous assemblies with branched morphology. A cryo-electron microscopy structure of NINJ1 filaments shows a tightly packed fence-like array of transmembrane α-helices. Filament directionality and stability is defined by two amphipathic α-helices that interlink adjacent filament subunits. The NINJ1 filament features a hydrophilic side and a hydrophobic side, and molecular dynamics simulations show that it can stably cap membrane edges. The function of the resulting supramolecular arrangement was validated by site-directed mutagenesis. Our data thus suggest that, during lytic cell death, the extracellular α-helices of NINJ1 insert into the plasma membrane to polymerize NINJ1 monomers into amphipathic filaments that rupture the plasma membrane. The membrane protein NINJ1 is therefore an interactive component of the eukaryotic cell membrane that functions as an in-built breaking point in response to activation of cell death."}],"_id":"13096","status":"public","article_type":"original","scopus_import":"1","doi":"10.1038/s41586-023-05991-z","title":"Structural basis of NINJ1-mediated plasma membrane rupture in cell death","pmid":1}]