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Nat Commun. 2015 Dec 3;6:8781. doi: 10.1038/ncomms9781.

Asymmetric ring structure of Vps4 required for ESCRT-III disassembly.

Author information

1
Unit of Virus-Host Cell interactions (UVHCI), University of Grenoble Alpes, F-38042 Grenoble, France.
2
CNRS, UVHCI, 71 avenue des Martyrs, F-38042 Grenoble, France.
3
Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
4
European Molecular Biology Laboratory (EMBL), Grenoble Outstation, 71 avenue des Martyrs, F-38042 Grenoble, France.
5
Institut de Biologie Structurale (IBS), University of Grenoble Alpes, 71 avenue des Martyrs, F-38044 Grenoble, France.
6
CNRS, IBS, 71 avenue des Martyrs, F-38044 Grenoble, France.
7
CEA, IBS, 71 avenue des Martyrs F-38044 Grenoble, France.

Abstract

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.

PMID:
26632262
PMCID:
PMC4686814
DOI:
10.1038/ncomms9781
[Indexed for MEDLINE]
Free PMC Article

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