Mycobacterium tuberculosis Rv0991c Is a Redox-Regulated Molecular Chaperone.

The bacterial pathogen is the leading cause of death by an infectious disease among humans. Here, we describe a previously uncharacterized protein, Rv0991c, as a molecular chaperone that is activated by oxidation. Rv0991c has homologs in most bacterial lineages and appears to function analogously to the well-characterized redox-regulated chaperone Hsp33, despite a dissimilar protein sequence. Rv0991c is transcriptionally coregulated with and chaperone genes in , suggesting that Rv0991c functions with these chaperones in maintaining protein quality control. Supporting this hypothesis, we found that, like oxidized Hsp33, oxidized Rv0991c prevents the aggregation of a model unfolded protein and promotes its refolding by the Hsp70 chaperone system. Furthermore, Rv0991c interacts with DnaK and can associate with many other proteins. We therefore propose that Rv0991c, which we named "Ruc" (redox-regulated protein with unstructured C terminus), represents a founding member of a new chaperone family that protects and other species from proteotoxicity during oxidative stress. infections are responsible for more than 1 million deaths per year. Developing effective strategies to combat this disease requires a greater understanding of biology. As in all cells, protein quality control is essential for the viability of , which likely faces proteotoxic stress within a host. Here, we identify an protein, Ruc, that gains chaperone activity upon oxidation. Ruc represents a previously unrecognized family of redox-regulated chaperones found throughout the bacterial superkingdom. Additionally, we found that oxidized Ruc promotes the protein-folding activity of the essential Hsp70 chaperone system. This work contributes to a growing body of evidence that oxidative stress provides a particular strain on cellular protein stability.