Vps4 stimulatory element of the cofactor vta1 contacts the ATPase Vps4 α7 and α9 to stimulate ATP hydrolysis

Brian A. Davies, Andrew P. Norgan, Johanna A. Payne, Mary E. Schulz, Micah D. Nichols, Jason A. Tan, Zhaohui Xu, David J. Katzmann

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The endosomal sorting complexes required for transport (ESCRTs) function in a variety of membrane remodeling processes including multivesicular body sorting, abscission during cytokinesis, budding of enveloped viruses, and repair of the plasma membrane. Vps4 ATPase activity modulates ESCRT function and is itself modulated by its cofactor Vta1 and its substrate ESCRT-III. The carboxyl-terminal Vta1/SBP-1/Lip5 (VSL) domain of Vta1 binds to the Vps4 β-domain to promote Vps4 oligomerization- dependent ATP hydrolysis. Additionally, the Vps4 stimulatory element (VSE) of Vta1 contributes to enhancing Vps4 oligomerATPhydrolysis.TheVSEisalsorequiredforVta1-dependent stimulation of Vps4 by ESCRT-III subunits. However, the manner by which the Vta1 VSE contributes to Vps4 activation is unknown.Existingstructuraldatawereusedtogenerateamodelof the Vta1 VSE in complex with Vps4. This model implicated residues within the small ATPase associated with various activities (AAA) domain, specifically α-helices 7 and 9, as relevant contact sites. Rational generation of Vps4 mutants defective for VSE-mediated stimulation, as well as intergenic compensatory mutations, support the validity of this model. These findings have uncovered the Vps4 surface responsible for coordinating ESCRT-III-stimulated Vta1 input during ESCRT function and identified a novel mechanism of Vps4 stimulation.

Original languageEnglish (US)
Pages (from-to)28707-28718
Number of pages12
JournalJournal of Biological Chemistry
Volume289
Issue number41
DOIs
StatePublished - Oct 10 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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