title: Calmodulin's flexibility allows for promiscuity in its interactions with target proteins and peptides.
abstract: The small bilobal calcium regulatory protein calmodulin (CaM) activates numerous target enzymes in response to transient changes in intracellular calcium concentrations. Binding of calcium to the two helix-loop-helix calcium-binding motifs in each of the globular domains induces conformational changes that expose a methionine-rich hydrophobic patch on the surface of each domain of the protein, which it uses to bind to peptide sequences in its target enzymes. Although these CaM-binding domains typically have little sequence identity, the positions of several bulky hydrophobic residues are often conserved, allowing for classification of CaM-binding domains into recognition motifs, such as the 1-14 and 1-10 motifs. For calcium-independent binding of CaM, a third motif known as the IQ motif is also common. Many CaM-peptide complexes have globular conformations, where CaM's central linker connecting the two domains unwinds, allowing the protein to wrap around a single predominantly alpha-helical target peptide sequence. However, novel structures have recently been reported where the conformation of CaM is highly dissimilar to these globular complexes, in some instances with less than a full compliment of bound calcium ions, as well as novel stoichiometries. Furthermore, many divergent CaM isoforms from yeast and plant species have been discovered with unique calcium-binding and enzymatic activation characteristics compared to the single CaM isoform found in mammals.
authors.affiliation: Structural Biology Research Group, Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, AB, Canada.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Yamniuk
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Vogel
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002147:Calmodulin; D005656:Fungal Proteins; D010940:Plant Proteins; D020033:Protein Isoforms; D011506:Proteins; D002118:Calcium