Mol. Cell 70, 614–627 (2018)

Hypochlorous acid (HOCl) exerts its bactericidal activity through oxidation or chlorination of various residues, leading to protein unfolding and aggregation. To protect itself during HOCl stress, Escherichia coli employs holdases, which bind to unfolded proteins and prevent their aggregation. When the cell is no longer under stress, these holdases transfer their substrates to the DnaK/J/GrpE chaperone system for refolding. Goemans et al. have now identified a new player in the E. coli response to HOCl, CnoX, which is upregulated upon HOCl exposure. CnoX is activated by chlorination of several residues in its tetratricopeptide (TPR) domain, which increases the hydrophobicity of its surface and endows it with holdase activity for a broad range of substrates. Like other holdases, CnoX can cooperate with DnaK/J/GrpE to refold proteins, but, unlike other known holdases, it can also cooperate with GroEL/ES. In addition to the holdase function of the TPR domain, CnoX contains a thioredoxin (Trx) domain that can form mixed disulfide complexes with other proteins, protecting them from oxidation by HOCl. These dual protective functions of CnoX led the researchers to name it a “chaperedoxin,” thus defining a new protein family.

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Cell Press