Architecture of the synaptotagmin–snare machinery for neuronal exocytosis

• Autores: Qiangjun Zhou, Ying Lai, Taulant Bacaj, Minglei Zhao, Artem Y. Lyubimov, Monarin Uervirojnangkoorn
• Localización: Nature: International weekly journal of science, ISSN 0028-0836, Vol. 525, Nº 7567, 2015, págs. 62-67
• Idioma: inglés
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• Resumen

  • 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 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 side chains. The structures reveal 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 mouse hippocampal neuronal synapses and for Ca2+-triggered vesicle fusion in a reconstituted system. We propose that this interface forms before Ca2+ triggering, 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.