title: Asymmetric ring structure of Vps4 required for ESCRT-III disassembly.
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.
authors.affiliation: Unit of Virus-Host Cell interactions (UVHCI), University of Grenoble Alpes, F-38042 Grenoble, France.|CNRS, UVHCI, 71 avenue des Martyrs, F-38042 Grenoble, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Caillat
authors.affiliation: Unit of Virus-Host Cell interactions (UVHCI), University of Grenoble Alpes, F-38042 Grenoble, France.|CNRS, UVHCI, 71 avenue des Martyrs, F-38042 Grenoble, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Macheboeuf
authors.affiliation: Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Yuanfei
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Unit of Virus-Host Cell interactions (UVHCI), University of Grenoble Alpes, F-38042 Grenoble, France.|European Molecular Biology Laboratory (EMBL), Grenoble Outstation, 71 avenue des Martyrs, F-38042 Grenoble, France.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: McCarthy
authors.affiliation: Institut de Biologie Structurale (IBS), University of Grenoble Alpes, 71 avenue des Martyrs, F-38044 Grenoble, France.|CNRS, IBS, 71 avenue des Martyrs, F-38044 Grenoble, France.|CEA, IBS, 71 avenue des Martyrs F-38044 Grenoble, France.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Boeri-Erba
authors.affiliation: Unit of Virus-Host Cell interactions (UVHCI), University of Grenoble Alpes, F-38042 Grenoble, France.|CNRS, UVHCI, 71 avenue des Martyrs, F-38042 Grenoble, France.
authors.forename: Gregory
authors.initials: G
authors.lastname: Effantin
authors.affiliation: Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Heinrich G
authors.initials: HG
authors.lastname: Göttlinger
authors.affiliation: Unit of Virus-Host Cell interactions (UVHCI), University of Grenoble Alpes, F-38042 Grenoble, France.|CNRS, UVHCI, 71 avenue des Martyrs, F-38042 Grenoble, France.
authors.forename: Winfried
authors.initials: W
authors.lastname: Weissenhorn
authors.affiliation: Unit of Virus-Host Cell interactions (UVHCI), University of Grenoble Alpes, F-38042 Grenoble, France.|CNRS, UVHCI, 71 avenue des Martyrs, F-38042 Grenoble, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Renesto
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D019848:Gene Expression Regulation, Archaeal / Q000502:physiology; D015497:HIV-1 / Q000502:physiology; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D016943:Sulfolobaceae / Q000235:genetics / Q000378:metabolism*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D000255:Adenosine Triphosphate