Autoregulation of the yeast copper metallothionein gene depends on metal binding.

The yeast CUP1 gene product, copper metallothionein, acts to repress the basal transcription of its own structural gene. By creating a series of truncation and amino acid substitutions in CUP1, we show that the ability of the protein to autoregulate is directly correlated to its ability to bind and detoxify copper. These results support a model in which metallothionein controls the level of free intracellular copper available to interact with positive transcription factors. In addition, mutations in chemically equivalent cysteine residues were functionally dissimilar, suggesting that partial sites in the molecule are critical for the formation of the sulfur-metal cluster.