title: Relief of autoinhibition enhances Vta1 activation of Vps4 via the Vps4 stimulatory element.
abstract: The endosomal sorting complexes required for transport (ESCRTs) impact multiple cellular processes including multivesicular body sorting, abscission, and viral budding. The AAA-ATPase Vps4 is required for ESCRT function, and its full activity is dependent upon the co-factor Vta1. The Vta1 carboxyl-terminal Vta1 SBP1 Lip5 (VSL) domain stimulates Vps4 function by facilitating oligomerization of Vps4 into its active state. Here we report the identification of the Vps4 stimulatory element (VSE) within Vta1 that is required for additional stimulation of Vps4 activity in vitro and in vivo. VSE activity is autoinhibited in a manner dependent upon the unstructured linker region joining the amino-terminal microtubule interacting and trafficking domains and the carboxyl-terminal VSL domain. The VSE is also required for Vta1-mediated Vps4 stimulation by ESCRT-III subunits Vps60 and Did2. These results suggest that ESCRT-III binding to the Vta1 microtubule interacting and trafficking domains relieves linker region autoinhibition of the VSE to produce maximal activation of Vps4 during ESCRT function.
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Norgan
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Davies
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Ishara F
authors.initials: IF
authors.lastname: Azmi
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Schroeder
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Johanna A
authors.initials: JA
authors.lastname: Payne
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905,; Becker Middle School, Becker, Minnesota 55308, and.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Lynch
authors.affiliation: the Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Xu
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: David J
authors.initials: DJ
authors.lastname: Katzmann
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D055503:Protein Multimerization / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C511158:DID2 protein, S cerevisiae; D056827:Endosomal Sorting Complexes Required for Transport; D029701:Saccharomyces cerevisiae Proteins; C107528:VPS4 protein, S cerevisiae; C430215:VPS60 protein, S cerevisiae; C487285:VTA1 protein, S cerevisiae; D000251:Adenosine Triphosphatases
keywords: AAA-ATPase; ATPases; ESCRT; Endosomes; Multivesicular Body; Protein Sorting; Protein Turnover; Receptor Endocytosis; Vps4; Vta1