Shao X, Li C, Fernandez I, Zhang X, Südhof T C, Rizo J
Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas 75235, USA.
Neuron. 1997 Jan;18(1):133-42. doi: 10.1016/s0896-6273(01)80052-0.
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.
突触结合蛋白I是一种突触囊泡蛋白，被认为在神经递质释放过程中充当钙离子传感器。突触结合蛋白I的第一个C2结构域（C2A结构域）包含一个双分型钙离子结合基序，并以钙离子依赖的方式与膜融合复合物的核心成分 syntaxin相互作用。通过核磁共振光谱和定点诱变分析表明，这种相互作用是由C2A结构域钙离子结合位点周围碱性残基的协同作用介导的，并且是由钙离子结合引起的C2A结构域静电势变化驱动的。提出了一个模型，即突触结合蛋白在钙离子触发的突触囊泡胞吐作用中充当静电开关，通过与syntaxin的相互作用促进融合机制中的结构重排。
