5fd9
From Proteopedia
X-ray Crystal Structure of ESCRT-III Snf7 core domain (conformation B)
Structural highlights
FunctionSNF7_YEAST Required for the sorting and concentration of proteins resulting in the entry of these proteins into the invaginating vesicles of the multivesicular body (MVB). Acts a component of the ESCRT-III complex, which appears to be critical for late steps in MVB sorting, such as membrane invagination and final cargo sorting and recruitment of late-acting components of the sorting machinery. The MVB pathway requires the sequential function of ESCRT-O, -I,-II and -III complex assemblies. Appears to sequester MVB cargo. Recruits BRO1, which in turn recruits DOA4, which deubiquitinates cargos before their enclosure within MVB vesicles.[1] [2] Publication Abstract from PubMedThe endosomal sorting complexes required for transport (ESCRTs) constitute hetero-oligomeric machines that catalyze multiple topologically similar membrane-remodeling processes. Although ESCRT-III subunits polymerize into spirals, how individual ESCRT-III subunits are activated and assembled together into a membrane-deforming filament remains unknown. Here, we determine X-ray crystal structures of the most abundant ESCRT-III subunit Snf7 in its active conformation. Using pulsed dipolar electron spin resonance spectroscopy (PDS), we show that Snf7 activation requires a prominent conformational rearrangement to expose protein-membrane and protein-protein interfaces. This promotes the assembly of Snf7 arrays with ~30A periodicity into a membrane-sculpting filament. Using a combination of biochemical and genetic approaches, both in vitro and in vivo, we demonstrate that mutations on these protein interfaces halt Snf7 assembly and block ESCRT function. The architecture of the activated and membrane-bound Snf7 polymer provides crucial insights into the spatially unique ESCRT-III-mediated membrane remodeling. Structural basis for activation, assembly and membrane binding of ESCRT-III Snf7 filaments.,Tang S, Henne WM, Borbat PP, Buchkovich NJ, Freed JH, Mao Y, Fromme JC, Emr SD Elife. 2015 Dec 15;4. pii: e12548. doi: 10.7554/eLife.12548. PMID:26670543[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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