Synaptotagmin's role in neurotransmitter release likely involves Ca(2+)-induced conformational transition.

ABSTRACT: Neuronal exocytosis is mediated by a Ca(2+)-triggered membrane fusion event that joins synaptic vesicles and presynaptic membrane. In this event, synaptotagmin I plays a key role as a Ca(2+) sensor protein that binds to and bends the presynaptic membrane with its C2B domain, and thereby initiates membrane fusion. We report free energy calculations according to which C2B-induced membrane bending is preceded by a Ca(2+)- and membrane-dependent conformational transition. In this transition C2B attaches to the membrane, moves its C-terminal helix from the orientation seen in the available (but membrane-free) crystal/NMR structures as pointing away from the membrane (helix-up), to an orientation pointing toward the membrane (helix-down). In the C2B helix-down state, lipid tails in the proximal

SUBMITTER: Wu Z 

PROVIDER: S-EPMC4156666 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature