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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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Calcium / metabolism*
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Calcium-Binding Proteins*
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Circular Dichroism
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Glutathione Transferase
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Magnetic Resonance Spectroscopy
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Membrane Fusion
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Membrane Glycoproteins / chemistry*
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Membrane Glycoproteins / metabolism*
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Membrane Proteins / chemistry*
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Membrane Proteins / metabolism*
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Models, Molecular
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Mutagenesis, Site-Directed
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Nerve Tissue Proteins / chemistry*
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Nerve Tissue Proteins / metabolism*
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Point Mutation
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Protein Conformation*
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Protein Denaturation
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Protein Structure, Secondary
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Qa-SNARE Proteins
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Static Electricity
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Synaptotagmin I
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Synaptotagmins
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Thermodynamics
Substances
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Calcium-Binding Proteins
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Membrane Glycoproteins
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Membrane Proteins
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Nerve Tissue Proteins
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Qa-SNARE Proteins
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Recombinant Fusion Proteins
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Synaptotagmin I
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Synaptotagmins
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Glutathione Transferase
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Calcium