Title | A direct role for the Sec1/Munc18-family protein Vps33 as a template for SNARE assembly. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Baker, RW, Jeffrey, PD, Zick, M, Phillips, BP, Wickner, WT, Hughson, FM |
Journal | Science |
Volume | 349 |
Issue | 6252 |
Pagination | 1111-4 |
Date Published | 2015 Sep 04 |
ISSN | 1095-9203 |
Keywords | Crystallography, X-Ray, Membrane Proteins, Munc18 Proteins, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, Qa-SNARE Proteins, R-SNARE Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Synaptosomal-Associated Protein 25, Vesicular Transport Proteins |
Abstract | <p>Fusion of intracellular transport vesicles requires soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) and Sec1/Munc18-family (SM) proteins. Membrane-bridging SNARE complexes are critical for fusion, but their spontaneous assembly is inefficient and may require SM proteins in vivo. We report x-ray structures of Vps33, the SM subunit of the yeast homotypic fusion and vacuole protein-sorting (HOPS) complex, bound to two individual SNAREs. The two SNAREs, one from each membrane, are held in the correct orientation and register for subsequent complex assembly. Vps33 and potentially other SM proteins could thus act as templates for generating partially zipped SNARE assembly intermediates. HOPS was essential to mediate SNARE complex assembly at physiological SNARE concentrations. Thus, Vps33 appears to catalyze SNARE complex assembly through specific SNARE motif recognition. </p> |
DOI | 10.1126/science.aac7906 |
Alternate Journal | Science |
PubMed ID | 26339030 |
PubMed Central ID | PMC4727825 |
Grant List | GM23377 / GM / NIGMS NIH HHS / United States T32 GM007388 / GM / NIGMS NIH HHS / United States R01 GM071574 / GM / NIGMS NIH HHS / United States GM071574 / GM / NIGMS NIH HHS / United States R01 GM023377 / GM / NIGMS NIH HHS / United States |