Structural basis of Ist1 function and Ist1-Did2 interaction in the multivesicular body pathway and cytokinesis

Junyu Xiao, Xiao Wei Chen, Brian A. Davies, Alan R. Saltiel, David J Katzmann, Zhaohui Xu

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

The ESCRT machinery functions in several important eukaryotic cellular processes. The AAA-ATPase Vps4 catalyzes disassembly of the ESCRT-III complex and may regulate membrane deformation and vesicle scission as well. Ist1 was proposed to be a regulator of Vps4, but its mechanism of action was unclear. The crystal structure of the N-terminal domain of Ist1 (Ist1NTD) reveals an ESCRT-III subunit-like fold, implicating Ist1 as a divergent ESCRT-III family member. Ist1NTD specifically binds to the ESCRT-III subunit Did2, and cocrystallization of Ist1NTD with a Did2 fragment shows that Ist1 interacts with the Did2 C-terminal MIM1 (MIT-interacting motif 1) via a novel MIM-binding structural motif. This arrangement indicates a mechanism for intermolecular ESCRT-III subunit association and may also suggest one form of ESCRT-III subunit autoinhibition via intramolecular interaction.

Original languageEnglish (US)
Pages (from-to)3514-3524
Number of pages11
JournalMolecular Biology of the Cell
Volume20
Issue number15
DOIs
StatePublished - Aug 1 2009

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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