Architecture of the synaptotagmin-SNARE machinery for neuronal exocytosis
| Autor: | Zhou, Qiangjun, Lai, Ying, Bacaj, Taulant, Zhao, Minglei, Lyubimov, Artem Y, Uervirojnangkoorn, Monarin, Zeldin, Oliver B, Brewster, Aaron S, Sauter, Nicholas K, Cohen, Aina E, Soltis, S Michael, Alonso-Mori, Roberto, Chollet, Matthieu, Lemke, Henrik T, Pfuetzner, Richard A, Choi, Ucheor B, Weis, William I, Diao, Jiajie, Südhof, Thomas C, Brunger, Axel T |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
General Science & Technology
1.1 Normal biological development and functioning Electrons Hippocampus Membrane Fusion Synaptic Transmission Exocytosis Mice Synaptotagmins Models Animals Magnesium Neurons Crystallography Binding Sites Lasers Cell Membrane Neurosciences Molecular Biological Generic Health Relevance Mutation X-Ray Calcium Synaptic Vesicles SNARE Proteins |
| Zdroj: | Zhou, Q; Lai, Y; Bacaj, T; Zhao, M; Lyubimov, AY; Uervirojnangkoorn, M; et al.(2015). Architecture of the synaptotagmin-SNARE machinery for neuronal exocytosis. Nature, 525(7567), 62-67. doi: 10.1038/nature14975. Lawrence Berkeley National Laboratory: Retrieved from: http://www.escholarship.org/uc/item/6ct9z2c1 Nature, vol 525, iss 7567 |
| DOI: | 10.1038/nature14975. |
| Popis: | © 2015 Macmillan Publishers Limited. 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. |
| Databáze: | OpenAIRE |
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