Structural highlights
FunctionPublication Abstract from PubMedIn many gram-positive Actinobacteria, including Actinomyces oris and Corynebacterium matruchotii, the conserved thiol-disulfide oxidoreductase MdbA that catalyzes oxidative folding of exported proteins is essential for bacterial viability by an unidentified mechanism. Intriguingly, in Corynebacterium diphtheriae, the deletion of mdbA blocks cell growth only at 37 degrees C but not at 30 degrees C, suggesting the presence of alternative oxidoreductase enzyme(s). By isolating spontaneous thermotolerant revertants of the mdbA mutant at 37 degrees C, we obtained genetic suppressors, all mapped to a single T-to-G mutation within the promoter region of tsdA, causing its elevated expression. Strikingly, increased expression of tsdA-via suppressor mutations or a constitutive promoter-rescues the pilus assembly and toxin production defects of this mutant, hence compensating for the loss of mdbA. Structural, genetic, and biochemical analyses demonstrated TsdA is a membrane-tethered thiol-disulfide oxidoreductase with a conserved CxxC motif that can substitute for MdbA in mediating oxidative folding of pilin and toxin substrates. Together with our observation that tsdA expression is upregulated at nonpermissive temperature (40 degrees C) in wild-type cells, we posit that TsdA has evolved as a compensatory thiol-disulfide oxidoreductase that safeguards oxidative protein folding in C. diphtheriae against thermal stress. A cryptic oxidoreductase safeguards oxidative protein folding in Corynebacterium diphtheriae.,Reardon-Robinson ME, Nguyen MT, Sanchez BC, Osipiuk J, Ruckert C, Chang C, Chen B, Nagvekar R, Joachimiak A, Tauch A, Das A, Ton-That H Proc Natl Acad Sci U S A. 2023 Feb 21;120(8):e2208675120. doi: , 10.1073/pnas.2208675120. Epub 2023 Feb 14. PMID:36787356[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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