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

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Science  04 Sep 2015:
Vol. 349, Issue 6252, pp. 1111-1114
DOI: 10.1126/science.aac7906

Unravelling the SM-SNARE conundrum

So-called SNARE proteins mediate and lend specificity to the fusion between different intracellular membranes. The SM proteins are universally required for intracellular vesicle fusion, yet their mechanism of action has long been enigmatic. Baker et al. have solved a piece of the puzzle by “capturing” SNAREs in the process of assembling into fusogenic complexes on the surface of an SM protein. The findings suggest exactly how and why SM proteins help vesicular fusion during intracellular membrane trafficking.

Science, this issue p. 1111


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.

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