5CCH

Structure of the Ca2+-bound synaptotagmin-1 SNARE complex (short unit cell form)

Summary for 5CCH

• Entry DOI: 10.2210/pdb5cch/pdb
• Related: 5CCG 5CCI
• Descriptor: Vesicle-associated membrane protein 2, Syntaxin-1A, Synaptosomal-associated protein 25, ... (6 entities in total)
• Functional Keywords: synaptic fusion complex, synaptotagmin1, neuronal snare complex, endocytosis, exocytosis
• Biological source: Rattus norvegicus (Rat); More
• Cellular location: Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Single-pass type IV membrane protein: P63045 P32851; Cytoplasm, perinuclear region : P60881 P60881; Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Single-pass membrane protein: P21707
• Total number of polymer chains: 6
• Total formula weight: 96345.44

Authors

Zhou, Q.,Zhao, M.,Lyubimov, A.Y.,Uervirojnangkoorn, M.,Zeldin, O.B.,Weis, W.I.,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 (3.6 Å)