text: Binding of Ca by the EF-hands causes an opening of the N- and C-domains, which exposes hydrophobic target-binding surfaces.  These surfaces interact with complementary nonpolar segments on target proteins, typically consisting of groups of bulky hydrophobic amino acids separated by 10–16 polar and/or basic amino acids.  The flexible central domain of calmodulin allows the protein to wrap around its target, although alternate modes of binding are known.  "Canonical" targets of calmodulin, such as myosin light-chain kinases and CaMKII, bind only to the Ca-bound protein, whereas some proteins, such as NaV channels and IQ-motif proteins, also bind to calmodulin in the absence of Ca.  Binding of calmodulin induces conformational rearrangements in the target protein via "mutually induced fit", leading to changes in the target protein's function.
  Calcium binding by calmodulin exhibits considerable cooperativity, making calmodulin an unusual example of a monomeric (single-chain) cooperative binding protein.  Furthermore, target binding alters the binding affinity of calmodulin toward Ca ions, which allows for complex allosteric interplay between Ca and target binding interactions.  This influence of target binding on Ca affinity is believed to allow for Ca activation of proteins that are constitutively bound to calmodulin, such as small-conductance Ca-activated potassium (SK) channels.
  Although calmodulin principally operates as a Ca binding protein, it also coordinates other metal ions. For example, in the presence of typical intracellular concentrations of Mg (0.5–1.0 mM) and resting concentrations of Ca (100 nM), calmodulins Ca binding sites are at least partially saturated by Mg. This Mg is displaced by the higher concentrations of Ca generated by signaling events. Similarly, Ca may itself be displaced by other metal ions, such as the trivalent lanthanides, that associate with calmodulins binding pockets even more strongly than Ca. Though such ions distort calmodulins structure and are generally not physiologically relevant due to their scarcity in vivo', they have nonetheless seen wide scientific use as reporters of calmodulin structure and function.