Synaptotagmin-5
calcium ion binding
Structural analysis of Ca<sup>2+</sup>-binding pocket of synaptotagmin 5 C2A domain.
Synaptotagmins constitute a family of multifunctional integral membrane proteins found predominantly on vesicles in neural and endocrine tissues. 17 isoforms of synaptotagmin family in mammals have been identified, 7 isoforms among them are known to be able to bind Ca<sup>2+</sup> via their C2 domains. This study presents the crystal structure of the first C2 domain (C2A domain) of synaptotagmin 5 complexed with Ca<sup>2+</sup> at 1.90Å resolution. Comparison of the Ca<sup>2+</sup>-binding pocket of synaptotagmin 5 C2A domain with other synaptotagmin C2 domains demonstrated that a serine residue locating at Ca<sup>2+</sup>-binding loop probably responsible to the conformational variation of Ca<sup>2+</sup>-binding pocket, and thus impacts the Ca<sup>2+</sup>-binding mechanism of C2 domain, which is verified by structural analysis of the serine mutant and Ca<sup>2+</sup>-binding assays via isothermal titration calorimetry. Alteration of Ca<sup>2+</sup>-binding mechanism might be correlated with different Ca<sup>2+</sup> response rates of synaptotagmins, which is the basis of the functions of synaptotagmins in regulating various types of Ca<sup>2+</sup>-triggered vesicle-membrane fusion processes.