Ca2+-Free Calmodulin Picture created with RasMac v2.6 PDB ID=1DMO	Calmodulin is an intracellular calcium receptor found ubiquitously in eukaryotes.  It is capable of regulating biological activities of many cellular proteins and transmembrane ion transporters mainly in a Ca2+-dependent manner.  When the intracellular calcium level rises to 10-5 M, four Ca2+ ions bind to calmodulin, and this Ca2+-calmodulin complex binds the target proteins, initiating various signalling cascades.
Calmodulin has four EF-hand motifs that change conformation upon binding calcium ions. Each EF-hand motif contains two alpha helices connected by a 12-residue loop. The calcium ion binds to the loop region and changes the relative positions of the alpha helices (Yap et al, 1999). In absence of calcium, the alpha-helices in the EF-hand motif of calmodulin are positioned almost parallel to each other. This is known as the closed conformation.

Upon binding Ca2+, calmodulin undergoes large conformational changes. The crystal structure of Ca2+-loaded calmodulin exhibits a dumbbell shape (Babu et al., 1985, Babu et al., 1988). However, it was later found that part of the central linker region of Ca2+-bound calmodulin is flexible in solution (Barbato et al, 1992).

Ca2+-bound Calmodulin Picture created with RasMac v2.6 PDB ID=3CLN

Both x-ray and NMR studies agree that the alpha helices of the EF-hand motifs change their position relative to each other, forming an almost perpendicular conformation (open conformation). This radical change allows calmodulin to increase its binding affinity for a number of target proteins. Gerstein and Krebs (1998) has a web site with movies that illustrate how calmodulin changes its conformation.

It has been shown through numerous structural studies that upon binding its target peptides, CaM forms a compact globular conformation by bending its central helix. Three calmodulin-binding peptides that have been studied so far (skeletal and smooth muscle myosin light chain kinases and calmodulin-dependent kinase II) form an alpha-helical conformation which passes through the middle of calmodulin, much like two hands holding onto a rope.
	Ca2+-bound Calmodulinwith rabbit skMLCK Picture created with RasMac v2.6 PDB ID=2BBM