Structural basis of Vta1 function in the multivesicular body sorting pathway

Dev Cell. 2008 Jan;14(1):37-49. doi: 10.1016/j.devcel.2007.10.013.

Abstract

The MVB pathway plays essential roles in several eukaryotic cellular processes. Proper function of the MVB pathway requires reversible membrane association of the ESCRTs, a process catalyzed by Vps4 ATPase. Vta1 regulates the Vps4 activity, but its mechanism of action was poorly understood. We report the high-resolution crystal structures of the Did2- and Vps60-binding N-terminal domain and the Vps4-binding C-terminal domain of S. cerevisiae Vta1. The C-terminal domain also mediates Vta1 dimerization and both subunits are required for its function as a Vps4 regulator. Emerging from our analysis is a mechanism of regulation by Vta1 in which the C-terminal domain stabilizes the ATP-dependent double ring assembly of Vps4. In addition, the MIT motif-containing N-terminal domain, projected by a long disordered linker, allows contact between the Vps4 disassembly machinery and the accessory ESCRT-III proteins. This provides an additional level of regulation and coordination for ESCRT-III assembly and disassembly.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Animals
  • Conserved Sequence
  • Crystallography, X-Ray
  • Endosomal Sorting Complexes Required for Transport
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Protein Conformation
  • Saccharomyces cerevisiae / chemistry*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Species Specificity
  • Vesicular Transport Proteins / chemistry*
  • Vesicular Transport Proteins / metabolism

Substances

  • Endosomal Sorting Complexes Required for Transport
  • Peptide Fragments
  • Saccharomyces cerevisiae Proteins
  • VTA1 protein, S cerevisiae
  • Vesicular Transport Proteins
  • Adenosine Triphosphate