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|Abstract:||Sec1/Munc18-family (SM) proteins are required for SNARE-mediated membrane fusion, but their mechanism(s) of action remain controversial. Using single-molecule force spectroscopy, we found that the SM protein Munc18-1 catalyzes step-wise zippering of three synaptic SNAREs (syntaxin, VAMP2, and SNAP-25) into a four-helix bundle. Catalysis requires formation of an intermediate template complex in which Munc18-1 juxtaposes the N-terminal regions of the SNARE motifs of syntaxin and VAMP2, while keeping their C-terminal regions separated. SNAP-25 binds the templated SNAREs to induce full SNARE zippering. Munc18-1 mutations modulate the stability of the template complex in a manner consistent with their effects on membrane fusion, indicating that chaperoned SNARE assembly is essential for exocytosis. Two other SM proteins, Munc18-3 and Vps33, similarly chaperone SNARE assembly via a template complex, suggesting that SM protein mechanism is conserved.|
|Citation:||Jiao, Junyi, He, Mengze, Port, Sarah A, Baker, Richard W, Xu, Yonggang, Qu, Hong, Xiong, Yujian, Wang, Yukun, Jin, Huaizhou, Eisemann, Travis J, Hughson, Frederick M, Zhang, Yongli. (2018). Munc18-1 catalyzes neuronal SNARE assembly by templating SNARE association.. eLife, 7 (10.7554/eLife.41771|
|Pages:||1 - 32|
|Type of Material:||Journal Article|
|Version:||Final published version. This is an open access article.|
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