Article abstract
Nature Structural & Molecular Biology 16, 754 - 762 (2009)
Published online: 14 June 2009 | doi:10.1038/nsmb.1621
Structural basis for ESCRT-III protein autoinhibition
Monika Bajorek1,2, Heidi L Schubert1,2, John McCullough1,2, Charles Langelier1, Debra M Eckert1, William-May B Stubblefield1, Nathan T Uter1, David G Myszka1, Christopher P Hill1 & Wesley I Sundquist1
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 
5 helices can fold back against the core domains. Mutations within the CHMP3 core–5 interface stimulate the protein's in vitro assembly and HIV-inhibition activities, indicating that dissociation of the autoinhibitory 5 helix from the core activates ESCRT-III proteins for assembly at membranes.
- Department of Biochemistry, University of Utah, Salt Lake City, Utah, USA.
- These authors contributed equally to this work.
Correspondence to: Christopher P Hill1 e-mail: chris@biochem.utah.edu
Correspondence to: Wesley I Sundquist1 e-mail: wes@biochem.utah.edu
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