| First Author | Zhou Q | Year | 2015 |
| Journal | Nature | Volume | 525 |
| Issue | 7567 | Pages | 62-7 |
| PubMed ID | 26280336 | Mgi Jnum | J:225864 |
| Mgi Id | MGI:5694851 | Doi | 10.1038/nature14975 |
| Citation | Zhou Q, et al. (2015) Architecture of the synaptotagmin-SNARE machinery for neuronal exocytosis. Nature 525(7567):62-7 |
| abstractText | Synaptotagmin-1 and neuronal SNARE proteins have central 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 Ca(2+)- and Mg(2+)-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 side chains. The structures reveal several interfaces, including a large, specific, Ca(2+)-independent and conserved interface. Tests of this interface by mutagenesis suggest that it is essential for Ca(2+)-triggered neurotransmitter release in mouse hippocampal neuronal synapses and for Ca(2+)-triggered vesicle fusion in a reconstituted system. We propose that this interface forms before Ca(2+) triggering, moves en bloc as Ca(2+) 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. |
