Structural changes in melittin and calmodulin upon complex formation and their modulation by calcium

In the presence of Ca2+, calmodulin forms a 1:1 high-affinity complex (Kd = 3 nM) with melittin, a peptide from bee venom; in the presence of ethylenediaminetetraacetic acid, a second type of complex, of much lower affinity, is formed [Comte, M., Maulet, Y., for instance the Ca2+-dependent high-affinity complex formation enhances the alpha-helical content of melittin from 5 to 72%. Provided Ca2+ is present, the interaction between the two peptides leads to significant changes in the environment of at least one tyrosine residue of calmodulin as measured by near-UV circular dichroism. In the absence of Ca2+, calmodulin binds two melittin molecules with a Kd of ca. 10 microM; at higher concentrations of free melittin, additional binding occurs (up to 5 mol of melittin/mol of calmodulin), with concomitant denaturation of calmodulin. In the presence of 4.0 M urea, the low-affinity complexes formed in the absence of Ca2+ dissociate, due to the denaturation of metal-free calmodulin, whereas the spectroscopic signals of the high-affinity Ca2+-dependent complex are not affected.(ABSTRACT TRUNCATED AT 250 WORDS)