Article abstract
Nature Structural & Molecular Biology 15, 1278 - 1286 (2008)
Published online: 9 November 2008 | doi:10.1038/nsmb.1512
Structural basis for midbody targeting of spastin by the ESCRT-III protein CHMP1B
Dong Yang1, Neggy Rismanchi2, Benoît Renvoisé2, Jennifer Lippincott-Schwartz3, Craig Blackstone2 & James H Hurley1
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-Å 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.
- Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland 20892, USA.
- Cellular Neurology Unit, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland 20892, USA.
- Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland 20892, USA.
Correspondence to: Craig Blackstone2 e-mail: blackstc@ninds.nih.gov
Correspondence to: James H Hurley1 e-mail: hurley@helix.nih.gov
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