ABSTRACT
Mammalian MTs consist of two domains designated P (N-terminal) and a (C-terminal). These two domains (Fig. 1) coordinate 7 divalent metal ions (Kagi 1991, Nielson et al. 1985, Nielson and Winge 1983,1985), into tetrahedral tetrathiolate clusters comprising 20 Cys residues (Fig. 1, Johnston et al. 1994, Glanville et al. 1981, Evans et al. 1990). The p-and adomains bind three and four bivalent metal ions, respectively. On the other hand, either domain binds 6 equivalents of monovalent ions such as Cu+ or Ag+ (Nielson et al. 1985, Nielson and Winge 1985). A certain selectivity of the MT domain for metal ions and the independent assembly of metal thiolate clusters were observed in the early work on MTs (Nielson and Winge 1983, 1984, 1985). Metal binding properties of the alpha and beta subunits of mouse MT 1 expressed in E. coli were characterized (Capdevila et al. 1997). The apparent affinity of the bacterially expressed mouse MT a-domain to bind cadmium is 1.8-fold stronger than the recombinant mMT-1 (Xiong et al. 1998). Similarly, the apparent cadmium binding of the alpha-fragment of human MT was approximately 12-fold
Figure 1. Coordination of divalent metal ions in the (i-and a-domains of class I metallothionein (MT). Mammalian MTs isolated from organisms exposed to Cd2* usually contain 5 Cd2* and 2 Zn2* atoms (Nielson et al. 1985, Nielson and Winge 1983) bound in tetrahedral tetrathiolate clusters (Kagi 1991). The affinity of particular metal binding centers (Ml to 7) for Cd2* (Kuraski et al. 19%) is indicated.
