Calcium binding site mutants of calmodulin adopt abnormal conformations in complexes with model target peptides.

We have examined the ability of two series of calcium binding site mutants of Drosophila calmodulin to form complexes with the model target peptides melittin and mastoparan. Unlike the wild-type complex, the 1:1 protein:melittin complexes formed by mutants of the C-terminal sites are unable to bind a second molecule of melittin. In contrast, a site 2 mutant shows increased ability to bind two molecules of melittin. For the shorter peptide mastoparan, most mutants form aberrant complexes that are best interpreted in terms of a model in which mastoparan interacts with both terminal domains of calmodulin. For two of the target enzymes of calmodulin, the three mutants which form mastoparan complexes most similar to the wild-type complex are also the best enzyme activators.