Coordination of substrate binding and ATP hydrolysis in Vps4-mediated ESCRT-III disassembly

Mol Biol Cell. 2010 Oct 1;21(19):3396-408. doi: 10.1091/mbc.E10-06-0512. Epub 2010 Aug 11.

Abstract

ESCRT-III undergoes dynamic assembly and disassembly to facilitate membrane exvagination processes including multivesicular body (MVB) formation, enveloped virus budding, and membrane abscission during cytokinesis. The AAA-ATPase Vps4 is required for ESCRT-III disassembly, however the coordination of Vps4 ATP hydrolysis with ESCRT-III binding and disassembly is not understood. Vps4 ATP hydrolysis has been proposed to execute ESCRT-III disassembly as either a stable oligomer or an unstable oligomer whose dissociation drives ESCRT-III disassembly. An in vitro ESCRT-III disassembly assay was developed to analyze Vps4 function during this process. The studies presented here support a model in which Vps4 acts as a stable oligomer during ATP hydrolysis and ESCRT-III disassembly. Moreover, Vps4 oligomer binding to ESCRT-III induces coordination of ATP hydrolysis at the level of individual Vps4 subunits. These results suggest that Vps4 functions as a stable oligomer that acts upon individual ESCRT-III subunits to facilitate ESCRT-III disassembly.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / metabolism*
  • Adenosine Triphosphate / metabolism*
  • Cell Membrane / metabolism
  • Endosomal Sorting Complexes Required for Transport / chemistry
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Hydrolysis
  • Models, Biological
  • Mutant Proteins / metabolism
  • Protein Stability
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Protein Subunits / metabolism
  • Protein Transport
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Substrate Specificity

Substances

  • Endosomal Sorting Complexes Required for Transport
  • Mutant Proteins
  • Protein Subunits
  • Saccharomyces cerevisiae Proteins
  • VPS4 protein, S cerevisiae
  • Adenosine Triphosphate
  • Adenosine Triphosphatases