STRUCTURE OF CALMODULIN TARGET PEPTIDE COMPLEXES

The structures of the complexes between calcium-bound calmodulin and synthetic peptides comprising the calmodulin-binding domain of skeletal and smooth muscle myosin light-chain kinase have now been solved by NMR and X-ray crystallography, respectively. Within coordinate errors, there are no significant differences between the two structures. The two domains of calmodulin (residues 6-73 and 83-146) remain essentially unchanged upon complexation. The long central helix (residues 65-93) which connects the two domains in the crystal structure of calcium-bound calmodulin, however, is disrupted in the complex into two helices connected by a long flexible loop (residues 74-82), thereby enabling the two domains to clamp the bound peptide which adopts a helical conformation. The overall structure of the complex is globular, approximating an ellipsoid of dimensions 47 x 32 x 30 angstrom The helical peptide is located in a hydrophobic channel which passes through the center of the ellipsoid at an angle of 45-degrees to its long axis.