Ca²⁺-dependent release of synaptotagmin-1 from the SNARE complex on phosphatidylinositol 4,5-bisphosphate-containing membranes.

ABSTRACT: The Ca²⁺ sensor synaptotagmin-1 and the SNARE complex cooperate to trigger neurotransmitter release. Structural studies elucidated three distinct synaptotagmin-1-SNARE complex binding modes involving 'polybasic', 'primary' and 'tripartite' interfaces of synaptotagmin-1. We investigated these interactions using NMR and fluorescence spectroscopy. Synaptotagmin-1 binds to the SNARE complex through the polybasic and primary interfaces in solution. Ca²⁺-free synaptotagmin-1 binds to SNARE complexes anchored on PIP₂-containing nanodiscs. R398Q/R399Q and E295A/Y338W mutations at the primary interface, which strongly impair neurotransmitter release, disrupt and enhance synaptotagmin-1-SNARE complex binding, respectively. Ca²⁺ induces tight binding of syn

SUBMITTER: Voleti R 

PROVIDER: S-EPMC7498268 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature