Synaptotagmin <p>Synaptotagmins are synaptic vesicle membrane proteins found in abundance in nerve cells and some endocrine cells [<cite idref="PUB00000918"/>, <cite idref="PUB00002879"/>]. The amino acid sequence of synaptotagmin comprises a single transmembrane region with a short vesicular N-terminal region, and a cytoplasmic C-terminal region containing 2 internal repeats similar to the C2 regulatory domain of protein kinase C. The protein is believed to be important in the docking and fusion of synaptic vesicles with the plasma membrane, i.e. with neurotransmitter release [<cite idref="PUB00000918"/>, <cite idref="PUB00002879"/>].</p><p>The 2 synaptotagmin C2 domains have been shown to have different functions: C2A binds phospholipid in a calcium-dependent manner, while C2B binds inositol polyphosphate and phospholipid irrespective of the presence of Ca²⁺ [<cite idref="PUB00002879"/>]. The structure of C2 domains in synaptotagmin I has been deduced: the C2 polypeptide forms an 8-stranded beta-sandwich constructed around a conserved 4-stranded motif, designated a C2 key [<cite idref="PUB00000918"/>]. The calcium binding region is a cup-shaped depression formed by the N- and C-terminal loops of the C2-key motif, while the site of phospholipid interaction is thought to be a polybasic sequence on the hairpin loop connecting strands 3 and 4 [<cite idref="PUB00000918"/>].</p>