@article{146926,
  keywords = {Animals, Humans, Rats, Neurons, Mutation, Protein Binding, Amino Acid Sequence, Sequence Homology, Amino Acid, Synaptosomal-Associated Protein 25, SNARE Proteins, Membrane Fusion, Munc18 Proteins, Exocytosis, Syntaxin 1, Vesicle-Associated Membrane Protein 2},
  author = {Junyi Jiao and Mengze He and Sarah Port and Richard Baker and Yonggang Xu and Hong Qu and Yujian Xiong and Yukun Wang and Huaizhou Jin and Travis Eisemann and Frederick Hughson and Yongli Zhang},
  title = {Munc18-1 catalyzes neuronal SNARE assembly by templating SNARE association},
  abstract = {<p>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.</p>
},
  year = {2018},
  journal = {Elife},
  volume = {7},
  pages = {e41771},
  month = {12/2018},
  issn = {2050-084X},
  doi = {10.7554/eLife.41771},
  language = {eng},
}