Calcium-induced conformational changes in the amino-terminal half of gelsolin

Gelsolin is an actin-binding protein that is regulated by the occupancy of multiple calcium-binding sites. We have studied calcium induced conformational changes in the G1–2 and G1–3 sub-domains, and report the binding affinities for the three type II sites. A new probe for G3 has been produced and a Kd of 5 μM has been measured for calcium in the context of G1–3. The two halves of gelsolin, G1–3 and G4–6 bind weakly with or without calcium, suggesting that once separated by apoptotic proteolysis, G1–3 and G4–6 remain apart allowing G1–3 to sever actin in a calcium free manner.