[2 Fe –2 S ] Oxidative‐Stress Sensor Sox R Bound to DNA

Abstract

SoxR, a member of the MerR (mercury resistance regulator) family, is a transcriptional activator that contains a [2Fe‐2S] cluster. In entric bacteria, SoxR functions as an oxidative‐stress sensor. However, in other nonentric bacteria, its physiological role appears to be different. SoxR is activated by reversible one‐electron oxidation of the [2Fe‐2S] cluster. In the active state, SoxR and other MerR family proteins activate transcription from unique promoters, which have a long 19 or 20 bp spacer between the −35 and −10 operator elements, by untwisting the promoter DNA. The crystal structures of SoxR and its complex with the target promoter in the oxidized (active) state have been reported. The structure of SoxR monomer consists of a winged helix‐turn helix DNA‐binding domain, a dimerization helix, and a Fe‐S cluster‐binding domain. The SoxR dimer is formed by an antiparallel long coiled coil. The [2Fe‐2S] cluster of SoxR is completely solvent‐exposed and surrounded by an asymmetric environment stabilized by interaction with the other subunit. The asymmetrically charged environment of the [2Fe‐2S] cluster probably causes redox‐dependent conformational changes of SoxR. The structure of the SoxR‐DNA complex provides a structural framework of the transcriptional activation by DNA distortion in the MerR family.