35] Escherichia coli SoxR protein: Sensor/transducer of oxidative stress and nitric oxide

Abstract

Publisher Summary The SoxR protein provides a unique example among iron-sulfur proteins: a transcription factor that is directly activated by oxidation of an [2Fe–2S] center without changing its DNA-binding affinity. The structural effects affect the structure of the bound soxS DNA to stimulate transcription and are paralleled by changes in cleavage produced by DNase I and other footprinting reagents. The Escherichia coli SoxR protein governs a cellular response to oxidative stress or nitric oxide (NO). SoxR activity in vitro is controlled by the oxidation state of the [2Fe–2S] centers, which undergo one-electron oxidation and reduction with a midpoint potential of –285 mV. In the reduced state, SoxR binds DNA without activating soxS transcription; oxidation unleashes SoxR transcriptional activity without affecting the DNA-binding affinity. Treatment of SoxR with nitric oxide nitrosylates the iron–sulfur centers, which also generate a strongly activated form of the protein. SoxR in vivo contains reduced [2Fe–2S] centers in the resting state, and the intracellular activation correlates perfectly with oxidation or nitrosylation). These activated forms of SoxR are eliminated rapidly, but the responsible reductase or other activities have not been identified. SoxR constitutes both the sensor of oxidative stress or nitric oxide and the transducer of these signals to gene expression.