Molecular mechanisms of action of calmodulin.

Publisher Summary This chapter focuses on the molecular mechanisms of action of the Ca2+ receptor calmodulin. It also summarizes the efforts to utilize the various biological reagents to elucidate the mechanism of action of calmodulin and some studies that provide insight into the mechanism of action of calmodulin at the molecular level. The crystal structure suggests that a central helix separates the two globular ends of the protein, each of which binds two Ca2+. Whether this helix exists in the solution is a matter of some controversy. Examination of this region by the ChaoFasman rules for protein structure predicts low stability for α helical formation in this region because of threonin (Thr) and serine (Ser). A further resolution of the crystal structure suggests that the pitch of the helix is offset by 10° because of the region containing these two residues. However, this region of the protein is changed upon Ca2+ binding. Proteolysis of calmodulin by trypsin results in different sites of cleavage in the absence of Ca2+ than when the Ca2+ sites are occupied. Insertion of amino acids in this central region alters the properties of enzyme activation by calmodulin. Studies on the interaction of the receptor with peptides derived from target proteins also show a role for this region. Therefore, the amino acid sequence between the two homologous halves of the protein is important for function, irrespective of a correct deduction of the shape of the protein in solution.