Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut, USA.
Nat Struct Mol Biol. 2011 Jul 24;18(8):927-33. doi: 10.1038/nsmb.2101.
Complexin prevents SNAREs from releasing neurotransmitters until an action potential arrives at the synapse. To understand the mechanism for this inhibition, we determined the structure of complexin bound to a mimetic of a prefusion SNAREpin lacking the portion of the v-SNARE that zippers last to trigger fusion. The 'central helix' of complexin is anchored to one SNARE complex, while its 'accessory helix' extends away at ~45° and bridges to a second complex, occupying the vacant v-SNARE binding site to inhibit fusion. We expected the accessory helix to compete with the v-SNARE for t-SNARE binding but found instead that the interaction occurs intermolecularly. Thus, complexin organizes the SNAREs into a zigzag topology that, when interposed between the vesicle and plasma membranes, is incompatible with fusion.
突触融合蛋白复合体通过阻止 SNARE 释放神经递质来抑制神经递质的释放，直到动作电位到达突触。为了理解这种抑制的机制，我们解析了与模拟融合前 SNARE 三聚体（缺乏能 zipper 最后引发融合的 v-SNARE 部分）结合的突触融合蛋白复合体的结构。突触融合蛋白复合体的“中心螺旋”锚定在一个 SNARE 三聚体上，而其“辅助螺旋”以约 45°的角度延伸，并桥接至第二个 SNARE 三聚体，占据空的 v-SNARE 结合位点以抑制融合。我们原本期望辅助螺旋会与 v-SNARE 竞争与 t-SNARE 的结合，但实际上发现这种相互作用是分子间的。因此，突触融合蛋白复合体将 SNARE 组装成之字形拓扑结构，当它位于囊泡和质膜之间时，与融合是不兼容的。
