A direct role for the Sec1/Munc18-family protein Vps33 as a template for SNARE assembly.

TitleA direct role for the Sec1/Munc18-family protein Vps33 as a template for SNARE assembly.
Publication TypeJournal Article
Year of Publication2015
AuthorsBaker, RW, Jeffrey, PD, Zick, M, Phillips, BP, Wickner, WT, Hughson, FM
JournalScience
Volume349
Issue6252
Pagination1111-4
Date Published2015 Sep 04
ISSN1095-9203
KeywordsCrystallography, 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>

DOI10.1126/science.aac7906
Alternate JournalScience
PubMed ID26339030
PubMed Central IDPMC4727825
Grant ListGM23377 / 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