C2 Protein Domain

The C2 domain is a region containing approximately 130 residues that is found in proteins that bind phospholipids in either a calcium-dependent or calcium-independent manner. C2 domains are found in over 100 different proteins with functions ranging from signal transduction to vesicular trafficking. Calcium binding to the C2 domain of synaptotagmin induces little conformational change in the C2 domain, but induces a change in electrostatic potential that enhances phospholipid binding. This suggests that the C2 domain functions as an electrostatic switch. In addition, side chains in the calcium binding loops influence the binding of different C2 domains to either neutral or negatively charged phospholipids.