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Calmodulin (CaM) (an abbreviation for CALcium-MODULated proteIN) is a calcium-binding messenger protein expressed in all eukaryotic cells. CaM is a multifunctional intermediate messenger protein that transduces calcium signals by binding calcium ions and then modifying its interactions with various target proteins.
CaM mediates many crucial processes such as inflammation, metabolism, apoptosis, smooth muscle contraction, intracellular movement, short-term and long-term memory, and the immune response. CaM is expressed in many cell types and can have different subcellular locations, including the cytoplasm, within organelles, or associated with the plasma or organelle membranes. Many of the proteins that CaM binds are unable to bind calcium themselves, and use CaM as a calcium sensor and signal transducer. CaM can also make use of the calcium stores in the endoplasmic reticulum, and the sarcoplasmic reticulum. CaM can undergo post-translational modifications, such as phosphorylation, acetylation, methylation and proteolytic cleavage, each of which has potential to modulate its actions.
Calmodulin is a small, highly conserved protein approximately 148 amino acids long (16706 Daltons). It contains four EF-hand motifs, each of which binds a Ca2+ ion. The protein has two approximately symmetrical globular domains (the N- and C-domain), separated by a flexible linker region. Calcium participates in an intracellular signalling system by acting as a diffusible second messenger to the initial stimuli.
Up to four calcium ions are bound by calmodulin via its four EF hand motifs. EF hands supply an electronegative environment for ion coordination. After calcium binding, hydrophobic methyl groups from methionine residues become exposed on the protein via conformational change. This presents hydrophobic surfaces, which can in turn bind to Basic Amphiphilic Helices (BAA helices) on the target protein. These helices contain complementary hydrophobic regions. The flexibility of Calmodulin's hinged region allows the molecule to "wrap around" its target. This property allows it to tightly bind to a wide range of different target proteins.
Dynamic features 
Compared to the X-ray crystal structure, the C-terminal domain solution structure is similar while the EF hands of the N-terminal domain are considerably less open. The backbone flexibility within calmodulin is key to its ability to bind a wide range of targets.
Family members 
- Calmodulin 1 (CALM1)
- Calmodulin 2 (CALM2)
- Calmodulin 3 (CALM3)
- Calmodulin-like 1 (CALML1)
- Calmodulin-like 3 (CALML3)
- Calmodulin-like 4 (CALML4)
- Calmodulin-like 5 (CALML5)
- Calmodulin-like 6 (CALML6)
Other calcium-binding proteins 
Calmodulin belongs to one of the two main groups of calcium-binding proteins, called EF hand proteins. The other group, called annexins, bind calcium and phospholipid (e.g., lipocortin). Many other proteins bind calcium, although binding calcium may not be considered their principal function in the cell.
See also 
- Proteopedia page for Calmodulin and its conformational change
- Protein kinase
- Ca2+/calmodulin-dependent protein kinase
- Stevens FC (1983). "Calmodulin: an introduction". Can. J. Biochem. Cell Biol. 61 (8): 906–10. doi:10.1139/o83-115. PMID 6313166.
- Chin D, Means AR (2000). "Calmodulin: a prototypical calcium sensor". Trends Cell Biol. 10 (8): 322–8. doi:10.1016/S0962-8924(00)01800-6. PMID 10884684.
- Chou JJ, Li S, Klee CB, Bax A (November 2001). "Solution structure of Ca(2+)-calmodulin reveals flexible hand-like properties of its domains". Nat. Struct. Biol. 8 (11): 990–7. doi:10.1038/nsb1101-990. PMID 11685248.
- RCSB details...
- Calmodulin at the US National Library of Medicine Medical Subject Headings (MeSH)
- Jennifer McDowall (2003-01-01). "Calmodulin". InterPro Protein Archive. Retrieved 2008-03-22.
- Melanie Nelson; Walter Chazin. "Home Page for Calmodulin". EF-Hand Calcium-Binding Proteins Data Library. Vanderbilt University. Retrieved 2008-03-22.
- Mitsuhiko Ikura. "Calmodulin Target Database". Ontario Cancer Institute, University of Toronto. Retrieved 2008-03-22.