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Calmodulin 3D structure

Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a calcium-binding messenger protein expressed in all eukaryotic cells. Calmodulin is a multifunctional intermediate messenger protein that transduces calcium signals by binding calcium ions and then modifying its interactions with various target proteins.[1][2]


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 148 amino acids long (16706 Daltons). The protein has two approximately symmetrical globular domains each containing a pair of EF-hand motifs (the N- and C-domain) separated by a flexible linker region. Each globular domain contains a pair of EF-hand motifs, which allows calmodulin to sense intracellular calcium levels by binding up to four Ca2+ ions. Calcium participates in an intracellular signaling 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. Using both X-Ray and NMR studies, scientists were able to determine that the conformational changes occured in the alpha-helices of the EF motif, which changes the binding affinity for target proteins. When the alpha helices are perpendicular to one another, the Calmodulin is in an open confirmation giving it a higher affinity for target proteins.[3] More specifically, this conformational change 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. The C-domain of calmodulin has a higher affinity for calcium than does the N-domain.

Dynamic features[edit]

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.[4] Protein domains, connected by intrinsically disordered flexible linker domains, induce long-range allostery via protein domain dynamics.

Family members[edit]

Other calcium-binding proteins[edit]

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[edit]


  1. ^ Stevens FC (1983). "Calmodulin: an introduction". Can. J. Biochem. Cell Biol. 61 (8): 906–10. doi:10.1139/o83-115. PMID 6313166. 
  2. ^ 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. 
  3. ^ "Calmodulin Target Database". Retrieved 2016-02-01. 
  4. ^ 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. 

External links[edit]