Structural Basis of Vta1 Function in the Multivesicular Body Sorting Pathway

Junyu Xiao, Hengchuan Xia, Jiahai Zhou, Ishara F. Azmi, Brian A. Davies, David J. Katzmann, Zhaohui Xu

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)37-49
Number of pages13
JournalDevelopmental Cell
Issue number1
StatePublished - Jan 15 2008



ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology


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