Ca(2+)-bridging mechanism and phospholipid head group recognition in the membrane-binding protein annexin V.

Structural evidence is presented for a 'Ca(2+)-bridging' mechanism, proposed for Ca(2+)-binding interfacial membrane proteins such as annexins, protein kinase C, and certain coagulation proteins. Crystal structures of Ca(2+)-annexin V complexes with phospholipid polar heads provide molecular details of 'Ca(2+)-bridges' as key features in the membrane attachment exhibited by these proteins. Distinct binding sites for phospholipid head groups are observed, including a novel, double-Ca2+ recognition site for phosphoserine that may serve as a phosphatidylserine receptor site in vivo.