Abstract
Endosomal sorting complexes required for transport-III (ESCRT-III) subunits cycle between two states: soluble monomers and higher-order assemblies that bind and remodel membranes during endosomal vesicle formation, midbody abscission and enveloped virus budding. Here we show that the N-terminal core domains of increased sodium tolerance-1 (IST1) and charged multivesicular body protein-3 (CHMP3) form equivalent four-helix bundles, revealing that IST1 is a previously unrecognized ESCRT-III family member. IST1 and its ESCRT-III binding partner, CHMP1B, both form higher-order helical structures in vitro, and IST1-CHMP1 interactions are required for abscission. The IST1 and CHMP3 structures also reveal that equivalent downstream alpha5 helices can fold back against the core domains. Mutations within the CHMP3 core-alpha5 interface stimulate the protein's in vitro assembly and HIV-inhibition activities, indicating that dissociation of the autoinhibitory alpha5 helix from the core activates ESCRT-III proteins for assembly at membranes.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Crystallography, X-Ray
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Cytokinesis / physiology
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Dimerization
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Endosomal Sorting Complexes Required for Transport
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Endosomes / metabolism
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Humans
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Models, Molecular
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Multiprotein Complexes / chemistry
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Multiprotein Complexes / metabolism
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Oncogene Proteins / chemistry*
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Oncogene Proteins / genetics
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Oncogene Proteins / metabolism*
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Protein Conformation*
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Protein Subunits / chemistry
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Protein Subunits / genetics
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Protein Subunits / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Vesicular Transport Proteins / chemistry*
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Vesicular Transport Proteins / genetics
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Vesicular Transport Proteins / metabolism*
Substances
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CHMP1B protein, human
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CHMP3 protein, human
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Endosomal Sorting Complexes Required for Transport
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IST1 protein, human
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Multiprotein Complexes
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Oncogene Proteins
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Protein Subunits
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Recombinant Proteins
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Vesicular Transport Proteins
Associated data
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PDB/3FRR
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PDB/3FRS
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PDB/3FRT
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PDB/3FRV