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

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.

SUBMITTER: Xiao J

PROVIDER: S-EPMC2719569 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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

Xiao Junyu J Chen Xiao-Wei XW Davies Brian A BA Saltiel Alan R AR Katzmann David J DJ Xu Zhaohui Z

Molecular biology of the cell 20090528 15

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 E ...[more]

PMID: 19477918

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