Interaction with adenylate cyclase toxin from affects the metal binding properties of calmodulin.

Adenylate cyclase toxin domain (CyaA-ACD) is a calmodulin (CaM)-dependent adenylate cyclase involved in pathogenesis. Calcium (Ca) and magnesium (Mg) concentrations impact CaM-dependent CyaA-ACD activation, but the structural mechanisms remain unclear. In this study, NMR, dynamic light scattering, and native PAGE were used to probe Mg-induced transitions in CaM's conformation in the presence of CyaA-ACD. Mg binding was localized to sites I and II, while sites III and IV remained Ca loaded when CaM was bound to CyaA-ACD. 2Mg/2Ca-loaded CaM/CyaA-ACD was elongated, whereas mutation of site I altered global complex conformation. These data suggest that CyaA-ACD interaction moderates CaM's Ca- and Mg-binding capabilities, which may contribute to pathobiology.