Zn- and Cu-thioneins: a functional classification for metallothioneins?

Abstract

This report intends to provide the reader with a deeper insight in the chemical, and extensively biological, characteristics of the metallothionein (MT) system. We have devoted nearly 20 years to the study of MTs and this has allowed us to form what we believe is a more complete picture of this peculiar family of metalloproteins. At the beginning of the 1990s, the landscape of this field was quite different from the overall picture we have now. Many researchers have contributed to the readjustment of this part of scientific knowledge. In our case, we implemented a unified method for obtaining MTs, for characterizing their metal-binding features, and for applying a unified research rationale. All this has helped to enlarge the initial picture that was mainly dominated by mammalian MT1/MT2 and yeast Cup1, by introducing approximately 20 new MTs. It has also allowed some characteristics to be clarified and examined in more detail, such as the cooperativity or the coexistence of multiple species in the metal-substitution reactions, the availability of Ag(I) or Cd(II) for use as respective probes for the Cu(I) and Zn(II) binding sites, the participation of chloride or sulfide ligands in the metal coordination spheres, and the feasibility of using in vitro data as representative of in vivo scenarios. Overall, the results yield enough data to consider new criteria for a proposal of classification of MTs based on MT metal-binding features, which complements the previous classifications, and that can shed light on the still controversial physiological functions of this peculiar superfamily of metalloproteins.

Contribution of ATPase copper transporters in animal but not plant virulence of the crossover pathogen Aspergillus flavus

“…In Saccharomyces cerevisiae , cells are protected from the toxic effects of excess Cu by protein metallothioneins that contain cysteine rich residues, detoxifying Cu by coordination with multiple Cu ions [46]. While metallothioneins appear to play the major role in Cu resistance in S. cerevisiae , a putative metallothionein, CrdA, identified in A. nidulans did not exhibit a role in Cu detoxification [22].…”

Barley Metallothioneins: MT3 and MT4 Are Localized in the Grain Aleurone Layer and Show Differential Zinc Binding

“…Concerning the functional properties of MTs, it is a puzzling aspect that the metal-binding preferences of the proteins apparently cannot be attributed to unique amino acids in the secondary structure (Palacios et al, 2011). Also, the lack of protein data derived from native plant MTs with respect to localization and metalprotein stoichiometry consistently hampers the characterization of plant MTs and the clarification of their metabolic roles.…”

The Copper Metallome in Eukaryotic Cells

“…Metallothioneins in mammals are responsible for the detoxi fi cation of cadmium, copper and zinc and have been proposed to be important in managing normal metal homeostasis [ 178,179 ] . The fi nal structure of metallated metallothioneins consists of two domains, an a and a b domain, de fi ned by the spacing of the cysteine residues and the number of metals coordinated.…”

“…The fi nal structure of metallated metallothioneins consists of two domains, an a and a b domain, de fi ned by the spacing of the cysteine residues and the number of metals coordinated. Metals bind in thiolate clusters that keep them in a biologically inert state [ 179 ] . Turnover of metallothionein occurs in the lysosome where the metals can be released back to the cytosol and some studies have suggested that metallothionein can be a direct source of metals for delivery within the cell independent of proteolysis [ 180 ] .…”