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Structural analysis and modeling reveals new mechanisms governing ESCRT-III spiral filament assembly

The scission of biological membranes is facilitated by a variety of protein complexes that bind and manipulate lipid bilayers. ESCRT-III (endosomal sorting complex required for transport III) filaments mediate membrane scission during the ostensibly disparate processes of multivesicular endosome bio...

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Autores principales: Shen, Qing-Tao, Schuh, Amber L., Zheng, Yuqing, Quinney, Kyle, Wang, Lei, Hanna, Michael, Mitchell, Julie C., Otegui, Marisa S., Ahlquist, Paul, Cui, Qiang, Audhya, Anjon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164947/
https://www.ncbi.nlm.nih.gov/pubmed/25202029
http://dx.doi.org/10.1083/jcb.201403108
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author Shen, Qing-Tao
Schuh, Amber L.
Zheng, Yuqing
Quinney, Kyle
Wang, Lei
Hanna, Michael
Mitchell, Julie C.
Otegui, Marisa S.
Ahlquist, Paul
Cui, Qiang
Audhya, Anjon
author_facet Shen, Qing-Tao
Schuh, Amber L.
Zheng, Yuqing
Quinney, Kyle
Wang, Lei
Hanna, Michael
Mitchell, Julie C.
Otegui, Marisa S.
Ahlquist, Paul
Cui, Qiang
Audhya, Anjon
author_sort Shen, Qing-Tao
collection PubMed
description The scission of biological membranes is facilitated by a variety of protein complexes that bind and manipulate lipid bilayers. ESCRT-III (endosomal sorting complex required for transport III) filaments mediate membrane scission during the ostensibly disparate processes of multivesicular endosome biogenesis, cytokinesis, and retroviral budding. However, mechanisms by which ESCRT-III subunits assemble into a polymer remain unknown. Using cryogenic electron microscopy (cryo-EM), we found that the full-length ESCRT-III subunit Vps32/CHMP4B spontaneously forms single-stranded spiral filaments. The resolution afforded by two-dimensional cryo-EM combined with molecular dynamics simulations revealed that individual Vps32/CHMP4B monomers within a filament are flexible and able to accommodate a range of bending angles. In contrast, the interface between monomers is stable and refractory to changes in conformation. We additionally found that the carboxyl terminus of Vps32/CHMP4B plays a key role in restricting the lateral association of filaments. Our findings highlight new mechanisms by which ESCRT-III filaments assemble to generate a unique polymer capable of membrane remodeling in multiple cellular contexts.
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spelling pubmed-41649472015-03-15 Structural analysis and modeling reveals new mechanisms governing ESCRT-III spiral filament assembly Shen, Qing-Tao Schuh, Amber L. Zheng, Yuqing Quinney, Kyle Wang, Lei Hanna, Michael Mitchell, Julie C. Otegui, Marisa S. Ahlquist, Paul Cui, Qiang Audhya, Anjon J Cell Biol Research Articles The scission of biological membranes is facilitated by a variety of protein complexes that bind and manipulate lipid bilayers. ESCRT-III (endosomal sorting complex required for transport III) filaments mediate membrane scission during the ostensibly disparate processes of multivesicular endosome biogenesis, cytokinesis, and retroviral budding. However, mechanisms by which ESCRT-III subunits assemble into a polymer remain unknown. Using cryogenic electron microscopy (cryo-EM), we found that the full-length ESCRT-III subunit Vps32/CHMP4B spontaneously forms single-stranded spiral filaments. The resolution afforded by two-dimensional cryo-EM combined with molecular dynamics simulations revealed that individual Vps32/CHMP4B monomers within a filament are flexible and able to accommodate a range of bending angles. In contrast, the interface between monomers is stable and refractory to changes in conformation. We additionally found that the carboxyl terminus of Vps32/CHMP4B plays a key role in restricting the lateral association of filaments. Our findings highlight new mechanisms by which ESCRT-III filaments assemble to generate a unique polymer capable of membrane remodeling in multiple cellular contexts. The Rockefeller University Press 2014-09-15 /pmc/articles/PMC4164947/ /pubmed/25202029 http://dx.doi.org/10.1083/jcb.201403108 Text en © 2014 Shen et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Shen, Qing-Tao
Schuh, Amber L.
Zheng, Yuqing
Quinney, Kyle
Wang, Lei
Hanna, Michael
Mitchell, Julie C.
Otegui, Marisa S.
Ahlquist, Paul
Cui, Qiang
Audhya, Anjon
Structural analysis and modeling reveals new mechanisms governing ESCRT-III spiral filament assembly
title Structural analysis and modeling reveals new mechanisms governing ESCRT-III spiral filament assembly
title_full Structural analysis and modeling reveals new mechanisms governing ESCRT-III spiral filament assembly
title_fullStr Structural analysis and modeling reveals new mechanisms governing ESCRT-III spiral filament assembly
title_full_unstemmed Structural analysis and modeling reveals new mechanisms governing ESCRT-III spiral filament assembly
title_short Structural analysis and modeling reveals new mechanisms governing ESCRT-III spiral filament assembly
title_sort structural analysis and modeling reveals new mechanisms governing escrt-iii spiral filament assembly
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164947/
https://www.ncbi.nlm.nih.gov/pubmed/25202029
http://dx.doi.org/10.1083/jcb.201403108
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