2lha
Solution structure of C2B with IP6
Structural highlights
FunctionSYT1_HUMAN 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 PubMedSynaptotagmin I is a synaptic vesicle membrane protein that serves as a multifunctional regulator during the exocytosis of neurotransmitter release. It contains C2A and C2B domains. The binding of Ca(2+) to the C2A domain activates the exocytosis of secretory vesicles, while the binding of inositol polyphosphates (IP4-IP6) to the C2B domain inhibits this process. To understand the IP6-induced inhibition of exocytosis of secretory vesicles, we determined the three-dimensional structure of the C2B-IP6 complex by nuclear magnetic resonance (NMR). In this study, we have determined the binding constant by isothermal titration calorimetry. The circular dichroism measurements demonstrated that IP6 can stabilize the C2B molecule. We identified the binding site using (1)H-(15)N heteronuclear single-quantum coherence spectroscopy titration data and determined the structure of the C2B-IP6 complex using multidimensional NMR studies. This information will aid in the design of better pharmacological treatments for neurological disorders. Molecular Level Interaction of Inositol Hexaphosphate with the C2B Domain of Human Synaptotagmin I.,Joung MJ, Mohan SK, Yu C Biochemistry. 2012 May 1;51(17):3675-83. Epub 2012 Apr 18. PMID:22475172[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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