Munc13 binds and recruits SNAP25 to chaperone SNARE complex assembly

AbstractSynaptic vesicle fusion is mediated by SNARE proteins ‐ VAMP2 on the vesicle and Syntaxin‐1/SNAP25 on the pre‐synaptic membrane. Chaperones Munc18‐1 and Munc13‐1 co‐operatively catalyze SNARE assembly via an intermediate ‘template’ complex containing Syntaxin‐1 and VAMP2. How SNAP25 enters this reaction remains a mystery. Here we repo rt that Munc13‐1 recruits SNAP25 to initiate the ternary SNARE complex assembly by direct binding, as judged by bulk FRET spectroscopy and single‐molecule optical tweezer studies. Detailed structure‐function analyses show that the binding is mediated by the Munc13‐1 MUN domain and is specifi c for the SNAP25 ‘linker’ region that connects the two SNARE motifs. Consequently, freely diffusing SNAP25 molecules on phospholipid bilayers are concentrated and bound in ~1:1 stoichiometry by the self‐assembled Munc13‐1 nano‐clusters.

Source: FEBS Letters - November 22, 2020 Category: Biochemistry Authors: R Venkat Kalyana Sundaram, Huaizhou Jin, Feng Li, Tong Shu, Jeff Coleman, Jie Yang, Frederic Pincet, Yongli Zhang, James E. Rothman, Shyam S. Krishnakumar Tags: RESEARCH ARTICLES Source Type: research