Partial Metal Ion Saturation of C2 Domains Primes Synaptotagmin 1-Membrane Interactions.

ABSTRACT: Synaptotagmin 1 (Syt1) is an integral membrane protein whose phospholipid-binding tandem C2 domains, C2A and C2B, act as Ca²⁺ sensors of neurotransmitter release. Our objective was to understand the role of individual metal-ion binding sites of these domains in the membrane association process. We used Pb²⁺, a structural and functional surrogate of Ca²⁺, to generate the protein states with well-defined protein-metal ion stoichiometry. NMR experiments revealed that binding of one divalent metal ion per C2 domain results in loss of conformational plasticity of the loop regions, potentially pre-organizing them for additional metal-ion and membrane-binding events. In C2A, a divalent metal ion in site 1 is sufficient to drive its weak association with phosphatid

SUBMITTER: Katti S 

PROVIDER: S-EPMC7091512 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature