Calmodulin

For an organism to function its cells must communicate with one another. This is done through direct contact or by means of signals delivered by an electrical impulse or a chemical messenger. Any signal employs a receiver; a protein is this receiver in the case of chemical messengers, that senses the arrival of the messenger and interprets the message by regulating the particular cellular activity. Calmodulin is a calcium-regulated protein , 16,700 kD, found in all eukaryotes.The calcium ions' importance as a cell regulator was first noticed by a British physiologist Sydney Ringer in 1883. He noticed that muscle contraction could be maintained in an isolated frog heart only if the ion is present in the medium surrounding the heart. It is now known that the calcium ion affects almost all aspects of cellular physiology.
Calmodulin has four calcium-binding domains which organize the proteins shape in response to the concentration of calcium. This in turn regulates its activity. At low Ca concentrations, calmodulin is inactive; only when the intracellular calcium ion concentration is increased to higher than 10-6 M does the binding equilibrium favor the fully bound form in which the protein assumes a more helical conformation "dumbbell" type structure shown above. The calcium binding segments consist of residues 20-31, 56-67, 93-104 and 129-140. All of these contain 12 residues; the first 9 form the loop and the last three the begining of the second helix in the helix-loop-helix domain.  This is an EF Hand protein, so-called because the folded helices (the E and F helices) resemble a hand with index finger and thumb extended. There are many Ca binding proteins with this structural motif.
The calcium binding domains in calmodulin are joined by linker segments composed of six residues . A hydrophobic patch on the surface of linking helix (the "bar") binds with a target enzyme to form an activated complex with the dumbell wrapped around its substrate. Because of this binding interaction the enzyme is turned on. Calmodulin is vital to cell functioning; any mutation resulting in a large change of the structure may be lethal to the cell.