Munc18-1 catalyzes neuronal SNARE assembly by templating SNARE association

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

Research output: Contribution to journalArticlepeer-review

94 Scopus citations


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.

Original languageEnglish (US)
Article numbere41771
StatePublished - Dec 1 2018

All Science Journal Classification (ASJC) codes

  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
  • General Neuroscience


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