Cargando…
Asymmetric ring structure of Vps4 required for ESCRT-III disassembly
The vacuolar protein sorting 4 AAA–ATPase (Vps4) recycles endosomal sorting complexes required for transport (ESCRT-III) polymers from cellular membranes. Here we present a 3.6-Å X-ray structure of ring-shaped Vps4 from Metallosphera sedula (MsVps4), seen as an asymmetric pseudohexamer. Conserved ke...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686814/ https://www.ncbi.nlm.nih.gov/pubmed/26632262 http://dx.doi.org/10.1038/ncomms9781 |
_version_ | 1782406504257683456 |
---|---|
author | Caillat, Christophe Macheboeuf, Pauline Wu, Yuanfei McCarthy, Andrew A. Boeri-Erba, Elisabetta Effantin, Gregory Göttlinger, Heinrich G. Weissenhorn, Winfried Renesto, Patricia |
author_facet | Caillat, Christophe Macheboeuf, Pauline Wu, Yuanfei McCarthy, Andrew A. Boeri-Erba, Elisabetta Effantin, Gregory Göttlinger, Heinrich G. Weissenhorn, Winfried Renesto, Patricia |
author_sort | Caillat, Christophe |
collection | PubMed |
description | The vacuolar protein sorting 4 AAA–ATPase (Vps4) recycles endosomal sorting complexes required for transport (ESCRT-III) polymers from cellular membranes. Here we present a 3.6-Å X-ray structure of ring-shaped Vps4 from Metallosphera sedula (MsVps4), seen as an asymmetric pseudohexamer. Conserved key interface residues are shown to be important for MsVps4 assembly, ATPase activity in vitro, ESCRT-III disassembly in vitro and HIV-1 budding. ADP binding leads to conformational changes within the protomer, which might propagate within the ring structure. All ATP-binding sites are accessible and the pseudohexamer binds six ATP with micromolar affinity in vitro. In contrast, ADP occupies one high-affinity and five low-affinity binding sites in vitro, consistent with conformational asymmetry induced on ATP hydrolysis. The structure represents a snapshot of an assembled Vps4 conformation and provides insight into the molecular motions the ring structure undergoes in a concerted action to couple ATP hydrolysis to ESCRT-III substrate disassembly. |
format | Online Article Text |
id | pubmed-4686814 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46868142016-01-02 Asymmetric ring structure of Vps4 required for ESCRT-III disassembly Caillat, Christophe Macheboeuf, Pauline Wu, Yuanfei McCarthy, Andrew A. Boeri-Erba, Elisabetta Effantin, Gregory Göttlinger, Heinrich G. Weissenhorn, Winfried Renesto, Patricia Nat Commun Article The vacuolar protein sorting 4 AAA–ATPase (Vps4) recycles endosomal sorting complexes required for transport (ESCRT-III) polymers from cellular membranes. Here we present a 3.6-Å X-ray structure of ring-shaped Vps4 from Metallosphera sedula (MsVps4), seen as an asymmetric pseudohexamer. Conserved key interface residues are shown to be important for MsVps4 assembly, ATPase activity in vitro, ESCRT-III disassembly in vitro and HIV-1 budding. ADP binding leads to conformational changes within the protomer, which might propagate within the ring structure. All ATP-binding sites are accessible and the pseudohexamer binds six ATP with micromolar affinity in vitro. In contrast, ADP occupies one high-affinity and five low-affinity binding sites in vitro, consistent with conformational asymmetry induced on ATP hydrolysis. The structure represents a snapshot of an assembled Vps4 conformation and provides insight into the molecular motions the ring structure undergoes in a concerted action to couple ATP hydrolysis to ESCRT-III substrate disassembly. Nature Publishing Group 2015-12-03 /pmc/articles/PMC4686814/ /pubmed/26632262 http://dx.doi.org/10.1038/ncomms9781 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Caillat, Christophe Macheboeuf, Pauline Wu, Yuanfei McCarthy, Andrew A. Boeri-Erba, Elisabetta Effantin, Gregory Göttlinger, Heinrich G. Weissenhorn, Winfried Renesto, Patricia Asymmetric ring structure of Vps4 required for ESCRT-III disassembly |
title | Asymmetric ring structure of Vps4 required for ESCRT-III disassembly |
title_full | Asymmetric ring structure of Vps4 required for ESCRT-III disassembly |
title_fullStr | Asymmetric ring structure of Vps4 required for ESCRT-III disassembly |
title_full_unstemmed | Asymmetric ring structure of Vps4 required for ESCRT-III disassembly |
title_short | Asymmetric ring structure of Vps4 required for ESCRT-III disassembly |
title_sort | asymmetric ring structure of vps4 required for escrt-iii disassembly |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686814/ https://www.ncbi.nlm.nih.gov/pubmed/26632262 http://dx.doi.org/10.1038/ncomms9781 |
work_keys_str_mv | AT caillatchristophe asymmetricringstructureofvps4requiredforescrtiiidisassembly AT macheboeufpauline asymmetricringstructureofvps4requiredforescrtiiidisassembly AT wuyuanfei asymmetricringstructureofvps4requiredforescrtiiidisassembly AT mccarthyandrewa asymmetricringstructureofvps4requiredforescrtiiidisassembly AT boerierbaelisabetta asymmetricringstructureofvps4requiredforescrtiiidisassembly AT effantingregory asymmetricringstructureofvps4requiredforescrtiiidisassembly AT gottlingerheinrichg asymmetricringstructureofvps4requiredforescrtiiidisassembly AT weissenhornwinfried asymmetricringstructureofvps4requiredforescrtiiidisassembly AT renestopatricia asymmetricringstructureofvps4requiredforescrtiiidisassembly |