Calmodulin is a small protein (Mr ~17,000) which contains four calcium ion binding sites (Figure 13.20). Each site binds Ca⁺⁺ with a KD of about 10^-6 M, consistent with observations that calcium can effect intracellular metabolic changes in concentrations as low as 1 mM.

Binding of calcium stimulates a major conformational change in the protein, leading to a more compact and more highly helical structure, which augments the affinity of calmodulin for a number of regulatory target proteins.

When bound to calcium, calmodulin plays a special role as an integral subunit of the glycogen metabolism enzyme, phosphorylase b kinase. Hence, the glycogenolysis cascade depends on intracellular calcium concentration as well as on cyclic AMP levels. This dependence is particularly important in muscle, where contraction is stimulated by calcium release. Thus, Ca⁺⁺ plays a dual role, in provision of the energy substrates needed to support muscle contraction and in contraction itself.

In addition to phosphorylase b kinase, the calmodulin-calcium complex binds to other proteins, including the myosin light chain kinase in muscle, which helps to stimulate muscular contraction.