Calmodulin is a small (148
residue)
regulatory protein that binds to a range of different targets. It is
activated by calcium, which is a common
secondary messenger in the cell. Ion binding is mostly through the sidechain
glu and
asx groups, although there is a backbone
carbonyl interaction.
It is often said to have a dumbbell (or barbell) shape. That is, it has two 'lobes' connected by a central helix. Each lobe binds two calcium ions with two EF hands. Indeed there is a symmetry axis across the central helix, as you might expect. The simplest description of the fold would be that it is four helix-turn-helix patterns fused together. The central helix is a concatenation of the last helix of the second HTH and the first helix of the third HTH. In fully bound structures, this central helix breaks into two smaller parts.
The most interesting aspect of the protein is its change of shape on binding of a substrate. The binding occurs across the central region of the protein, and the structure folds itself around the ligand. In one sense, this 'change' is illusory; the unbound crystal structure shows the barbell shape, while the bound structure is compact. However, it is unlikely that the extended structure is stable, since the central helix is very solvent-exposed. It has been suggested that this stretched shape is an artifact of crystal packing.