6mti | pdb_00006mti
Synaptotagmin-1 C2A, C2B domains and SNARE-pin proteins (5CCI) individually docked into Cryo-EM map of C2AB-SNARE complexes helically organized on lipid nanotube surface in presence of Mg2+
Structural highlights
Function[SNP25_RAT] t-SNARE involved in the molecular regulation of neurotransmitter release. May play an important role in the synaptic function of specific neuronal systems. Associates with proteins involved in vesicle docking and membrane fusion. Regulates plasma membrane recycling through its interaction with CENPF. [STX1A_RAT] Potentially involved in docking of synaptic vesicles at presynaptic active zones. May play a critical role in neurotransmitter exocytosis. May mediate Ca(2+)-regulation of exocytosis acrosomal reaction in sperm. [SYT1_RAT] May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. It binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone. A Ca(2+)-dependent interaction between synaptotagmin and putative receptors for activated protein kinase C has also been reported. It can bind to at least three additional proteins in a Ca(2+)-independent manner; these are neurexins, syntaxin and AP2. [VAMP2_RAT] Involved in the targeting and/or fusion of transport vesicles to their target membrane (By similarity). Publication Abstract from PubMedSynapotagmin-1 (Syt1) interacts with both SNARE proteins and lipid membranes to synchronize neurotransmitter release to calcium (Ca(2+)) influx. Here we report the cryo-electron microscopy structure of the Syt1-SNARE complex on anionic-lipid containing membranes. Under resting conditions, the Syt1 C2 domains bind the membrane with a magnesium (Mg(2+))-mediated partial insertion of the aliphatic loops, alongside weak interactions with the anionic lipid headgroups. The C2B domain concurrently interacts the SNARE bundle via the 'primary' interface and is positioned between the SNAREpins and the membrane. In this configuration, Syt1 is projected to sterically delay the complete assembly of the associated SNAREpins and thus, contribute to clamping fusion. This Syt1-SNARE organization is disrupted upon Ca(2+)-influx as Syt1 reorients into the membrane, likely displacing the attached SNAREpins and reversing the fusion clamp. We thus conclude that the cation (Mg(2+)/Ca(2+)) dependent membrane interaction is a key determinant of the dual clamp/activator function of Synaptotagmin-1. Structural basis for the clamping and Ca(2+) activation of SNARE-mediated fusion by synaptotagmin.,Grushin K, Wang J, Coleman J, Rothman JE, Sindelar CV, Krishnakumar SS Nat Commun. 2019 Jun 3;10(1):2413. doi: 10.1038/s41467-019-10391-x. PMID:31160571[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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