Bipartite Ca 2+ -Binding Motif in C 2 Domains of Synaptotagmin and Protein Kinase C

C 2 domains are found in many proteins involved in membrane traffic or signal transduction. Although C 2 domains are thought to bind calcium ions, the structural basis for calcium binding is unclear. Analysis of calcium binding to C 2 domains of synaptotagmin I and protein kinase C-β by nuclear magnetic resonance spectroscopy revealed a bipartite calcium-binding motif that involves the coordination of two calcium ions by five aspartate residues located on two separate loops. Sequence comparisons indicated that this may be a widely used calcium-binding motif, designated here as the C 2 motif.