Mammalian metallothioneins

Mammalian metallothioneins typically bind seven metal ions in cluster structures, with bridging sulfur groups, as seen in the x-ray structure of the Cd5Zn2MT complex (86). It is therefore difficult to develop a simple formation-constant description for the binding of metal ions to MT (87), considering that protonation-deprotonation equilibria of the free protein itself should also be taken into account. However, the usefulness of Table VIII as a guide to the affinity of metal ions for mercapto donor ligands is seen in that the ability of metal ions to... 

Comparative studies on amino acid sequences of 12 mammalian metallothioneins have been reported.1457 They are all similar and contain 61 residues JV-acetylmethionine and alanine are at the N and C termini, respectively. The cysteinyl residues are distributed fairly uniformly along the polypeptide chain with a predominance of —Cys—X—Cys— sequences. 

The amino acid sequences of many mammalian metallothioneins are known.1152 They all contain 61 residues with the cysteine residues distributed along the full length of the polypeptide chain, and with N-acetylmethionlne and alanine at the N- and C-termini, respectively. All 20 cysteine residues are involved in the binding of up to seven metal ions via thiolate linkages. A typical amino acid sequence is shown in Figure 44. 

Miles AT, Hawksworth GM, Beattie JH, Rodilla V (2000) Induction, regulation, degradation, and biological significance of mammalian metallothioneins. Crit Rev Biochem Mol Biol 35 35-70... 

Metallothionein proteins are the most abundant intracellular, metal-binding proteins (Andrews, 2000). Four metallothionein isoforms have been identified in the mouse (MT-I-MT-IV) and are clustered within 50 kilobases of each other. In humans, there is one MTII gene and a cluster of MT I genes on chromosome 16 (Searl et al., 1984 West et al., 1990 Heuchel et al., 1995). The mammalian metallothioneins generally consist of 61 amino acids and 20 of these are cysteines (Heuchel et al., 1995). These cysteines are important for the binding of such bivalent metal ions, such as zinc, copper and cadmium. 

Norey, C.G., W.E. Lees, B.M. Darke, et al. 1990. Immunological distinction between piscine and mammalian metallothioneins. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 95 597-601. 

Figure 7 The (a) and a (b) cadmium-thiolate domain structures in mammalian metallothionein. Yellow spheres represent Cys-sulfurs and Green spheres represent Cd(ll) atoms. Based on models developed in our laboratory, for example, Ref. 41...

Tio L, Villarreal L, Atrian S, and Capdevila M (2004) Functional differentiation in the mammalian metallothionein gene family, metal binding features of mouse MT4 and comparison with its paralog MTl. Journal of... 

Lefebvre, D., B. Miki, and J. Laliberte, Mammalian metallothionein functions in plants. Bio-technology, 1987 5 1053-1056. 

Fig. 6.1 Model of the molecular structure of mammalian metallothionein, showing the primary sequence, and two topologically separate metal-thiolate clusters. (After Otvos and Armitage 1980.)...

Fig. 6.2 Three-dimensional structure of the metallic domains of the complex of CdyMT, and primary model of mammalian metallothionein.

The amino acid sequences of many mammalian metallothioneins are known. They all contain... 

Vasak M, Mcloni G (2011) Chemistry and biology of mammalian metallothioneins. J Biol Inorg Chem 16 1067-1078... 

Tamai KT, Gralla EB, Ellerby LM, Valentine JS, Thiele DJ (1993) Yeast and mammalian metallothioneins functionally substitute for yeast copper-zinc superoxide dismutase. Proc Natl Acad Sci USA 90 8013-8017... 

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