Solution structure of Ca2+-calmodulin reveals flexible hand-like properties of its domains

The solution structure of Ca2+-ligated calmodulin is determined from residu al dipolar couplings measured in a liquid crystalline medium and from a lar ge number of heteronuclear J couplings for defining side chains. Although t he C-terminal domain solution structure is similar to the X-ray crystal str ucture, the EF hands of the N-terminal domain are considerably less open. T he substantial differences in interhelical angles correspond to negligible changes in short interproton distances and, therefore, cannot be identified by comparison of NOEs and X-ray data. NOE analysis, however, excludes a tw o-state equilibrium in which the closed apo conformation is partially popul ated in the Ca2+-ligated state. The difference between the crystal and solu tion structures of Ca2+-calmodulin indicates considerable backbone plastici ty within the domains of calmodulin, which is key to their ability to bind a wide range of targets. In contrast, the vast majority of side chains maki ng up the target binding surface are locked into the same chi (1) rotameric states as in complexes with target peptide.