SigR (σ R ) is a sigma factor responsible for inducing the thioredoxin system in response to oxidative stress in the antibiotic-producing, Gram-positive bacterium Streptomyces coelicolor A3(2). Here we identify a redoxsensitive, σ R -specific anti-sigma factor, RsrA, which binds σ R and inhibits σ R -directed transcription in vitro only under reducing conditions. Exposure to H 2 O 2 or to the thiol-specific oxidant diamide caused the dissociation of the σ R -RsrA complex, thereby allowing σ R -dependent transcription. This correlated with intramolecular disulfide bond formation in RsrA. Thioredoxin was able to reduce oxidized RsrA, suggesting that σ R , RsrA and the thioredoxin system comprise a novel feedback homeostasis loop that senses and responds to changes in the intracellular thiol-disulfide redox balance.

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1The various chaperone activities of heat shock proteins contribute to ensuring 2 cellular proteostasis. Here, we demonstrate the non-canonical unfoldase activity as 3 an inherent functionality of the prokaryotic molecular chaperone Hsp33. The holding-4 inactive, reduced form of Hsp33 ( R Hsp33) strongly bound to the translational 5 elongation factor, EF-Tu, and catalyzed the EF-Tu aggregation via evoking its 6 aberrant folding, resulting in its susceptibility to proteolytic degradation by Lon. This 7 interaction was critically mediated by the redox-switch domain of R Hsp33 and the 8 guanine nucleotide-binding domain of EF-Tu. The R Hsp33-induced in vivo 9 aggregation of EF-Tu upon heat shock was evident in a Lon-deficient strain and 10 inhibited cell growth. Unlike wild-type Escherichia coli, the strain lacking both Hsp33 11 and Lon showed a non-reduced level of EF-Tu and diminished capability of 12 counteracting heat shock. These findings suggest that the unique 13 unfoldase/aggregase activity of Hsp33 potentially involved in protein turnover confers 14 a cellular survival advantage under heat-stressed conditions.15 16