RsrAs

RsrA is a redox-sensitive anti-sigma factor found in actinomycetes, most notably in Streptomyces species, where it partners with the extracytoplasmic function sigma factor SigR to regulate the oxidative stress response. Under normal conditions, RsrA binds SigR and prevents transcription of SigR-dependent genes, helping to maintain redox balance by keeping the response in check. RsrA is a small cytosolic protein that coordinates a zinc ion through a cluster of cysteine residues, a feature that links its activity to the cell’s redox state.

The regulatory mechanism is redox-responsive. In the presence of oxidative or disulfide stress, the cysteine residues in RsrA become oxidized, promoting disulfide bond formation and Zn2+ release. This causes a conformational change that releases SigR, allowing SigR to associate with RNA polymerase and activate transcription of its regulon. The SigR regulon includes genes involved in thiol-redox homeostasis, such as thioredoxins and glutaredoxins, as well as other protective proteins that help mitigate oxidative damage. Once redox conditions return to baseline, RsrA is reduced and rebinds SigR, turning off the response in a negative feedback loop.

The RsrA–SigR system serves as a model of redox-regulated transcription in bacteria and contributes to oxidative stress tolerance and adaptive responses in Streptomyces and related actinomycetes. Its study provides insight into bacterial stress management and may influence understanding of antibiotic production linked to redox state in these organisms.