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Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Nature 2015 ; 525 (7567): 62-7 Nephropedia Template TP
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Architecture of the Synaptotagmin-SNARE Machinery for Neuronal Exocytosis #MMPMID26280336
Zhou Q; Lai Y; Bacaj T; Zhao M; Lyubimov AY; Uervirojnangkoorn M; Zeldin OB; Brewster AS; Sauter NK; Cohen AE; Soltis SM; Alonso-Mori R; Chollet M; Lemke HT; Pfuetzner RA; Choi UB; Weis WI; Diao J; Südhof TC; Brunger AT
Nature 2015[Sep]; 525 (7567): 62-7 PMID26280336show ga
Synaptotagmin-1 and neuronal SNARE proteins play key roles in evoked synchronous neurotransmitter release. However, it is unknown how they cooperate to trigger synaptic vesicle fusion. Here we report atomic-resolution crystal structures of Ca2+- and Mg2+-bound complexes between synaptotagmin-1 and the neuronal SNARE complex, one of which was determined with diffraction data from an X-ray free electron laser, leading to an atomic-resolution structure with accurate rotamer assignments for many sidechains. The structures revealed several interfaces, including a large, specific, Ca2+-independent, and conserved interface. Tests of this interface by mutagenesis suggest that it is essential for Ca2+-triggered neurotransmitter release in neuronal synapses and for Ca2+-triggered vesicle fusion in a reconstituted system. We propose that this interface forms prior to Ca2+-triggering, and moves en bloc as Ca2+ influx promotes the interactions between synaptotagmin-1 and the plasma membrane, and consequently remodels the membrane to promote fusion, possibly in conjunction with other interfaces.