5CCJ

Crystal structure of the quintuple mutant of the synaptotagmin-1 C2B domain

Summary for 5CCJ

• Entry DOI: 10.2210/pdb5ccj/pdb
• Descriptor: Synaptotagmin-1, GLYCEROL, SULFATE ION, ... (4 entities in total)
• Functional Keywords: synaptotagmin1, c2b domain, signaling protein
• Biological source: Rattus norvegicus (Rat)
• Cellular location: Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Single-pass membrane protein: P21707
• Total number of polymer chains: 4
• Total formula weight: 72671.13

Authors

Zhou, Q.,Zhao, M.,Brunger, A.T. (deposition date: 2015-07-02, release date: 2015-08-12, Last modification date: 2023-09-27)

Primary citation

Zhou, Q.,Lai, Y.,Bacaj, T.,Zhao, M.,Lyubimov, A.Y.,Uervirojnangkoorn, M.,Zeldin, O.B.,Brewster, A.S.,Sauter, N.K.,Cohen, A.E.,Soltis, S.M.,Alonso-Mori, R.,Chollet, M.,Lemke, H.T.,Pfuetzner, R.A.,Choi, U.B.,Weis, W.I.,Diao, J.,Sudhof, T.C.,Brunger, A.T.
Architecture of the synaptotagmin-SNARE machinery for neuronal exocytosis.
Nature, 525:62-67, 2015

PubMed Abstract: 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.

PubMed: 26280336
DOI: 10.1038/nature14975

Experimental method

X-RAY DIFFRACTION (1.65 Å)