Structural Basis for Midbody Targeting of Spastin by the ESCRT-III Protein CHMP1B

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2008 Nov 11

PMID 18997780

Citations 128

Authors

Dong Yang

Neggy Rismanchi

Benoit Renvoise

Jennifer Lippincott-Schwartz

Craig Blackstone

James H Hurley

Affiliations

Soon will be listed here.

Abstract

The endosomal sorting complex required for transport (ESCRT) machinery, including ESCRT-III, localizes to the midbody and participates in the membrane-abscission step of cytokinesis. The ESCRT-III protein charged multivesicular body protein 1B (CHMP1B) is required for recruitment of the MIT domain-containing protein spastin, a microtubule-severing enzyme, to the midbody. The 2.5-A structure of the C-terminal tail of CHMP1B with the MIT domain of spastin reveals a specific, high-affinity complex involving a noncanonical binding site between the first and third helices of the MIT domain. The structural interface is twice as large as that of the MIT domain of the VPS4-CHMP complex, consistent with the high affinity of the interaction. A series of unique hydrogen-bonding interactions and close packing of small side chains discriminate against the other ten human ESCRT-III subunits. Point mutants in the CHMP1B binding site of spastin block recruitment of spastin to the midbody and impair cytokinesis.

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