Calmodulin

Literature References: A calcium-binding multifunctional regulatory protein, ubiquitously distributed in eukaryotic cells. It functions as an intracellular intermediary for calcium ions and activates a number of enzymes involved in fundamental cell processes, such as protein phosphorylation, contractile processes, and metabolism of cyclic nucleotides, of glycogen and of calcium, as well as in other metabolic reactions. Originally discovered as a protein activator of cyclic 3¢,5¢-nucleotide phosphodiesterase: W. Y. Cheung, Biochem. Biophys. Res. Commun. 29, 478 (1967); idem, Biochim. Biophys. Acta 191, 303 (1969); idem, Biochem. Biophys. Res. Commun. 38, 533 (1970); S. Kakiuchi et al., ibid. 41, 1104 (1970). Calcium-binding activity: T. S. Teo, J. H. Wang, J. Biol. Chem. 248, 5950 (1973). Calmodulin is a relatively small, acidic, stable monomer of mol wt 15,000-19,000, lacking cysteine, hydroxyproline, and tryptophan. It has a high content of acidic amino acids and low tyrosine content; almost all calmodulins isolated also contain a single, fully trimethylated lysyl residue. Purification from bovine brain: Y. M. Lin et al., ibid. 249, 4943 (1974); eidem, Methods Enzymol. 39, Pt. C, 262 (1974). Amino acid sequence of CaM from bovine brain: T. C. Vanaman in Calcium Binding Proteins and Calcium Function, R. H. Wasserman et al., Eds. (Elsevier, New York, 1977) pp 107-116; D. M. Watterson et al., J. Biol. Chem. 255, 962 (1980); from rat testis: J. R. Dedman et al., ibid. 253, 343 (1978); from sea invertebrate, Renilla reniformis: T. C. Vanaman, F. Sharief, Fed. Proc. 38, 788 (1979). Radioimmunoassay: R. W. Wallace, W. Y. Cheung, J. Biol. Chem. 254, 6564 (1979); J. C. Chafouleas et al., ibid. 10262. CaM has four Ca2+-binding sites; binding to any one of the sites results in a conformational change, which is required for calmodulin to regulate enzyme systems. Conformational transition study: C. B. Klee, Biochemistry 16, 1017 (1977). An important feature of calmodulin's structure is the presence of four homologous internal amino acid sequences, called domains. Each of these domains (one for each bound calcium) are reportedly "E-F Hands", a structural concept described by R. H. Kretsinger in Calcium Transport in Contraction and Secretions, E. Carafoli et al., Eds. (Elsevier, Amsterdam, 1975) pp 469-478. Calmodulins obtained from a wide range of phylogenetically different sources are similar in amino acid sequence and in physicochemical and biological properties; hence, the protein lacks both species and tissue specificity and appears to be structurally and functionally conserved throughout evolution. Reviews: W. Y. Cheung, Science 207, 19-27 (1980); A. R. Means, J. R. Dedman, Nature 285, 73-77 (1980); C. B. Klee et al., Annu. Rev. Biochem. 49, 489-515 (1980); A. R. Means, Recent Prog. Horm. Res. 37, 333-367 (1981); Y. M. Lin, Mol. Cell. Biochem. 45, 101-112 (1982). Books: Ann. N.Y. Acad. Sci. 356, entitled "Calmodulin and Cell Functions", D. M. Watterson, F. F. Vincenzi, Eds. (1980) 455 pp; Calcium and Cell Function vol. 1, W. Y. Cheung, Ed. (Academic Press, New York, 1980) 395 pp.