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Synaptotagmin-syntaxin interaction: the C2 domain as a Ca2+-dependent electrostatic switch.

X Shao·C Li·I Fernandez·X Zhang·T C Südhof·J Rizo
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Abstract

Synaptotagmin I is a synaptic vesicle protein that is thought to act as a Ca2+ sensor in neurotransmitter release. The first C2 domain of synaptotagmin I (C2A domain) contains a bipartite Ca2+-binding motif and interacts in a Ca2+-dependent manner with syntaxin, a central component of the membrane fusion complex. Analysis by nuclear magnetic resonance spectroscopy and site-directed mutagenesis shows that this interaction is mediated by the cooperative action of basic residues surrounding the Ca2+-binding sites of the C2A domain and is driven by a change in the electrostatic potential of the C2A domain induced by Ca2+ binding. A model is proposed whereby synaptotagmin acts as an electrostatic switch in Ca2+-triggered synaptic vesicle exocytosis, promoting a structural rearrangement in the fusion machinery that is effected by its interaction with syntaxin.

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Amino Acid SequenceAnimalsBinding SitesCalciumCalcium-Binding ProteinsCircular DichroismGlutathione TransferaseMagnetic Resonance SpectroscopyMembrane FusionMembrane GlycoproteinsMembrane ProteinsModels, MolecularMutagenesis, Site-DirectedNerve Tissue ProteinsPoint MutationProtein ConformationProtein DenaturationProtein Structure, SecondaryQa-SNARE ProteinsRecombinant Fusion ProteinsStatic ElectricitySynaptotagmin ISynaptotagminsThermodynamicsJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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X Shao, C Li, I Fernandez, X Zhang, T C Südhof, J Rizo. 1997. Synaptotagmin-syntaxin interaction: the C2 domain as a Ca2+-dependent electrostatic switch.. https://doi.org/10.1016/s0896-6273(01)80052-0

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