Structure of human synaptotagmin 1 C2AB in the absence of Ca2+ reveals a novel domain association
Structure of human synaptotagmin 1 C2AB in the absence of Ca2+ reveals a novel domain association
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DOI：
10.1021/bi701651k
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发表时间：
2007-11-13
期刊：
影响因子：
2.9
通讯作者：
Sutton, R. Bryan
中科院分区：
文献类型：
--
作者：
Fuson, Kerry L.;Montes, Miguel;Sutton, R. Bryan
突触囊泡释放神经递质需要钙/磷脂结合蛋白syndptotagmin 1。有相当多的证据表明，突触结合蛋白的串联C2结构域之间的合作是调节胞吐作用的要求，然而，这种相互作用的高分辨率的结构证据一直缺乏。人突触结合蛋白I的胞质结构域的2.7埃的晶体结构，在没有Ca 2+的情况下，揭示了一种新的封闭构象的蛋白质。C2 A和C2B之间的共享界面通过C2B结构域的C-末端α-螺旋上的残基与C2 A的Ca 2+结合区的环1-3上的残基之间的相互作用网络来稳定。这些相互作用改变了C2 A的Ca 2+结合口袋的整体形状，但不是C2B。因此，突触结合蛋白I C2 A-C2B可以利用一种新的调节机制，其中一个C2结构域可以调节另一个，直到适当的触发事件使它们停止。
Release of neurotransmitter from synaptic vesicles requires the Ca2+/phospholipid-binding protein syndptotagmin 1. There is considerable evidence that cooperation between the tandem C2 domains of synaptotagmin is a requirement of regulated exocytosis; however, high-resolution structural evidence for this interaction has been lacking. The 2.7 angstrom crystal structure of the cytosolic domains of human synaptotagmin I in the absence of Ca2+ reveals a novel closed conformation of the protein. The shared interface between C2A and C2B is stabilized by a network of interactions between residues on the C-terminal alpha-helix of the C2B domain and residues on loops 1-3 of the Ca2+-binding region of C2A. These interactions alter the overall shape of the Ca2+-binding pocket of C2A, but not that of C2B. Thus, synaptotagmin I C2A-C2B may utilize a novel regulatory mechanism whereby one C2 domain could regulate the other until an appropriate triggering event decouples them.