Transcriptional regulation via redox-sensitive iron-sulphur centres in an oxidative stress response

Genetic responses to oxidative stress are triggered by excessive levels of agents such as superoxide. The soxRS regulon of Escherichia coli includes at least a dozen oxidative-stress and antibiotic-resistance genes that are activated by the SoxS protein, the synthesis of which is controlled by the redox-sensing SoxR protein. SoxR is a homodimer of 17 kDa subunits, each of which contains a [2Fe-2S] cluster. Transcriptional activation by SoxR is controlled by the oxidation state of these metal centres. In the absence of oxidative stress, the [2Fe-2S] centres are in the reduced form and the protein is inactive, although it still binds the soxS promoter. Agents that generate superoxide in the cell (e.g. paraquat) cause rapid oxidation of the metal centres, which triggers the transcriptional activity of SoxR; removal of the oxidative stress is followed by rapid re-reduction of the [2Fe-2S] centres. This facile mechanism links oxidation state to control of protein activity and may be used widely to allow cells to respond to oxidative stress.