Munc13 binds and recruits SNAP25 to chaperone SNARE complex assembly.

FEBS Letters
Ramalingam Venkat Kalyana SundaramShyam S Krishnakumar

Abstract

Synaptic vesicle fusion is mediated by SNARE proteins-VAMP2 on the vesicle and Syntaxin-1/SNAP25 on the presynaptic membrane. Chaperones Munc18-1 and Munc13-1 cooperatively catalyze SNARE assembly via an intermediate 'template' complex containing Syntaxin-1 and VAMP2. How SNAP25 enters this reaction remains a mystery. Here, we report 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 specific 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 nanoclusters.

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Citations

Apr 8, 2021·Annual Review of Biochemistry·Yongli Zhang, Frederick M Hughson
Aug 22, 2021·Journal of Molecular Biology·Rafayel PetrosyanMichael T Woodside
Nov 17, 2021·FEBS Letters·Lukas A Huber

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