Crystal Structure of the Cytosolic C2a-C2b Domains of Synaptotagmin III

By R B Sutton, J. Ernst, A. Brunger. 1999

Synaptotagmins are synaptic vesicle-associated, phospholipid-binding proteins most commonly associated with Ca+2-dependent exocytotic and Ca+2- independent endocytotic events. Synaptotagmin III is a 63.2-kD member of the synaptotagmin homology group; one of its characteristic properties is the ability to bind divalent cations and accessory proteins promiscuously. In the cytosolic portion of this protein, a flexible seven–amino acid linker joins two homologous C2 domains. The C2A domain binds to phospholipid membranes and other accessory proteins in a divalent cation-dependent fashion. The C2B domain promotes binding to other C2B domains, as well as accessory proteins independent of divalent cations. The 3.2 Å crystal structure of synaptotagmin III, residues 295–566, which includes the C2A and C2B domains, exhibits differences in the shape of the Ca+2-binding pocket, the electrostatic surface potential, and the stoichiometry of bound divalent cations for the two domains. These observations may explain the disparate binding properties of the two domains. The C2A and the C2B domains do not interact; synaptotagmin, therefore, covalently links two independent C2 domains, each with potentially different binding partners. A model of synaptotagmin's involvement in Ca+2-dependent regulation of membrane fusion through its interaction with the SNARE complex is presented.

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Citations in the corpus

Towards automated crystallographic structure refinement with phenix.refine (2012, background): “The re-refinement of a synaptotagmin structure at 3.2 Å resolution (PDB entry 1dqv; Sutton et al., 1999) emphasizes the importance of using a TLS parameterization not only as a way to reduce the number of refined parameters but more importantly to provide a more reasonable model for global domain…”
Biological basket weaving: formation and function of clathrin-coated vesicles. (2001, unknown): “…PH domain PDB ID, 2DYN (Timm et al. 1994); amphiphysin2 SH3 domain PDB ID, 1BB9 (Owen et al. 1998); synaptotagmin III C2A and C2B domains PDB ID, 1DQV (Sutton et al. 1999); Eps15 EH1 domain PDB ID, 1QJT (Whitehead et al. 1999); Eps15 EH2 domain with bound NPF-containing peptide PDB ID, 1FF1 (de…”
Mechanisms of membrane fusion: disparate players and common principles (2008, background): “It was the first synaptotagmin for which a crystal structure of the double C2-domain fragment was obtaine”
Secretory granule exocytosis. (2003, background): “In the synaptic complex, syntaxin (t-SNARE) contributes one Q-containing helix, SNAP-25 (t-SNARE) contributes two Q-containing helices, and VAMP (v-SNARE) contributes one R-containing helix (605, 743) (Fig.”