Unknown

Dataset Information

0

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


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.

SUBMITTER: Jiao J 

PROVIDER: S-EPMC6320071 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

Similar Datasets

2017-01-01 | S-EPMC5651683 | BioStudies
2011-01-01 | S-EPMC3162418 | BioStudies
1000-01-01 | S-EPMC3438936 | BioStudies
2020-01-01 | S-EPMC6969487 | BioStudies
2010-01-01 | S-EPMC2834481 | BioStudies
2010-01-01 | S-EPMC3012463 | BioStudies
2013-01-01 | S-EPMC3569727 | BioStudies
2017-01-01 | S-EPMC5470040 | BioStudies
2013-01-01 | S-EPMC3725074 | BioStudies
2015-01-01 | S-EPMC4668942 | BioStudies