Fernandez I, Ubach J, Dulubova I, Zhang X, Südhof T C, Rizo J
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Cell. 1998 Sep 18;94(6):841-9. doi: 10.1016/s0092-8674(00)81742-0.
Syntaxin 1A plays a central role in neurotransmitter release through multiple protein-protein interactions. We have used NMR spectroscopy to identify an autonomously folded N-terminal domain in syntaxin 1A and to elucidate its three-dimensional structure. This 120-residue N-terminal domain is conserved in plasma membrane syntaxins but not in other syntaxins, indicating a specific role in exocytosis. The domain contains three long alpha helices that form an up-and-down bundle with a left-handed twist. A striking residue conservation is observed throughout a long groove that is likely to provide a specific surface for protein-protein interactions. A highly acidic region binds to the C2A domain of synaptotagmin I in a Ca2+-dependent interaction that may serve as an electrostatic switch in neurotransmitter release.
Syntaxin 1A通过多种蛋白质-蛋白质相互作用在神经递质释放中起核心作用。我们利用核磁共振光谱法鉴定了Syntaxin 1A中一个自主折叠的N端结构域，并阐明了其三维结构。这个由120个残基组成的N端结构域在质膜Syntaxin中保守，但在其他Syntaxin中不保守，表明其在胞吐作用中具有特定作用。该结构域包含三个长的α螺旋，形成一个具有左手扭曲的上下束。在一个可能为蛋白质-蛋白质相互作用提供特定表面的长凹槽中观察到显著的残基保守性。一个高度酸性的区域在Ca2+依赖的相互作用中与突触结合蛋白I的C2A结构域结合，这可能在神经递质释放中作为一个静电开关。
