Munc18-1 catalyzes neuronal SNARE assembly by templating SNARE association

• DOI: 10.7554/elife.41771
• Publication Date: 2018-12-12T13:01:30Z
• Authors: Junyi Jiao; Mengze He; Sarah A Port; Richard W Baker; Yonggang Xu; Hong Qu; Yujian Xiong; Yukun Wang; Huaizhou Jin; Travis J Eisemann; Frederick M Hughson; Yongli Zhang
• Keywords: SNARE complex; Vesicular Transport Proteins; Tethering

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 three synaptic SNAREs (syntaxin, VAMP2, and SNAP-25) into a four-helix bundle. Catalysis requires formation an intermediate template complex in which juxtaposes N-terminal regions SNARE motifs syntaxin while keeping C-terminal separated. SNAP-25 binds templated to induce full zippering. mutations modulate stability manner consistent with effects on indicating chaperoned assembly is essential exocytosis. Two other proteins, Munc18-3 Vps33, similarly chaperone via complex, suggesting mechanism conserved.