The essential trace element copper is also highly toxic when accumulated at high intracellular levels. Copper detoxification in the yeasts S.cerevisiae and C.glabrata is carried out, in large part, by small, cysteine-rich metal binding proteins known as metallothioneins (MTs). The biosynthesis of yeast metallothioneins, the S.cerevisiae copper, zinc superoxide dismutase, and presumably other important copper homeostatic proteins, is transcriptionally induced by elevated environmental copper concentrations through the action of copper metalloregulatory transcription factors (MRTFs). Copper coordination drives the formation of a structure distinct from the apo-protein, whereupon the DNA binding function of MRTFs is activated. The copper MRTFs, ACE1 from S.cerevisiae and AMT1 from C.glabrata, directly interact with specific copper-responsive cis-acting elements in the promotor regions of their respective target genes. The binding of copper, as a polynuclear cluster, to MRTFs provides a sensitive and rapid means of transducing the extracellular metal signal to activate gene transcription.
