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From Proteopedia
Synaptotagmin-1 C2B domain with phosphoserine
Structural highlights
FunctionSYT1_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. Publication Abstract from PubMedSynaptic-vesicle exocytosis is mediated by the vesicular Ca(2+) sensor synaptotagmin-1. Synaptotagmin-1 interacts with the SNARE protein syntaxin-1A and acidic phospholipids such as phosphatidylinositol 4,5-bisphosphate (PIP2). However, it is unclear how these interactions contribute to triggering membrane fusion. Using PC12 cells from Rattus norvegicus and artificial supported bilayers, we show that synaptotagmin-1 interacts with the polybasic linker region of syntaxin-1A independent of Ca(2+) through PIP2. This interaction allows both Ca(2+)-binding sites of synaptotagmin-1 to bind to phosphatidylserine in the vesicle membrane upon Ca(2+) triggering. We determined the crystal structure of the C2B domain of synaptotagmin-1 bound to phosphoserine, allowing development of a high-resolution model of synaptotagmin bridging two different membranes. Our results suggest that PIP2 clusters organized by syntaxin-1 act as molecular beacons for vesicle docking, with the subsequent Ca(2+) influx bringing the vesicle membrane close enough for membrane fusion. Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment.,Honigmann A, van den Bogaart G, Iraheta E, Risselada HJ, Milovanovic D, Mueller V, Mullar S, Diederichsen U, Fasshauer D, Grubmuller H, Hell SW, Eggeling C, Kuhnel K, Jahn R Nat Struct Mol Biol. 2013 Jun;20(6):679-86. doi: 10.1038/nsmb.2570. Epub 2013 May, 12. PMID:23665582[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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