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Munc18-1 catalyzes neuronal SNARE assembly by templating SNARE association.

Author(s): Jiao, Junyi; He, Mengze; Port, Sarah A; Baker, Richard W; Xu, Yonggang; et al

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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.
Publication Date: 12-Dec-2018
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
DOI: doi:10.7554/eLife.41771
ISSN: 2050-084X
EISSN: 2050-084X
Pages: 1 - 32
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: eLife
Version: Final published version. This is an open access article.

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