Schematic depiction of the calcium-triggered activation of synaptotagmin. In the absence of calcium, the two C2 domains of synaptotagmin, C2A and C2B, are far apart and very little energy transfer is observed. Donor (W259) is represented by the white circle on C2A; acceptor (coumarin) is represented by the black circle on C2B. On calcium binding, C2A and C2B undergo an intramolecular association, bringing W259 on C2A and coumarin on C2B closer together, and the extent of energy transfer increases dramatically.