5W5D

Crystal structure of the primed SNARE-Complexin-Synaptotagmin-1 C2B complex

5W5D の概要

• エントリーDOI: 10.2210/pdb5w5d/pdb
• 分子名称: Vesicle-associated membrane protein 2, Syntaxin-1A, Synaptosomal-associated protein 25, ... (8 entities in total)
• 機能のキーワード: prefusion primed complex, neuronal exocytosis, synaptotagmin, snare complex, complexin, synchronous neurotransmitter release, exocytosis
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• 細胞内の位置: Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Single-pass type IV membrane protein: P63045 P32851; Cytoplasm, perinuclear region : P60881 P60881; Cytoplasm, cytosol : P63041; Cytoplasmic vesicle, secretory vesicle membrane ; Single-pass membrane protein : P21707
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 56033.07

構造登録者

Zhou, Q.,Brunger, A.T. (登録日: 2017-06-14, 公開日: 2017-08-23, 最終更新日: 2023-10-04)

主引用文献

Zhou, Q.,Zhou, P.,Wang, A.L.,Wu, D.,Zhao, M.,Sudhof, T.C.,Brunger, A.T.
The primed SNARE-complexin-synaptotagmin complex for neuronal exocytosis.
Nature, 548:420-425, 2017

PubMed Abstract: Synaptotagmin, complexin, and neuronal SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins mediate evoked synchronous neurotransmitter release, but the molecular mechanisms mediating the cooperation between these molecules remain unclear. Here we determine crystal structures of the primed pre-fusion SNARE-complexin-synaptotagmin-1 complex. These structures reveal an unexpected tripartite interface between synaptotagmin-1 and both the SNARE complex and complexin. Simultaneously, a second synaptotagmin-1 molecule interacts with the other side of the SNARE complex via the previously identified primary interface. Mutations that disrupt either interface in solution also severely impair evoked synchronous release in neurons, suggesting that both interfaces are essential for the primed pre-fusion state. Ca binding to the synaptotagmin-1 molecules unlocks the complex, allows full zippering of the SNARE complex, and triggers membrane fusion. The tripartite SNARE-complexin-synaptotagmin-1 complex at a synaptic vesicle docking site has to be unlocked for triggered fusion to start, explaining the cooperation between complexin and synaptotagmin-1 in synchronizing evoked release on the sub-millisecond timescale.

PubMed: 28813412
DOI: 10.1038/nature23484

実験手法

X-RAY DIFFRACTION (2.496 Å)