7UNN

Thiol-disulfide oxidoreductase TsdA from Corynebacterium diphtheriae

Summary for 7UNN

• Entry DOI: 10.2210/pdb7unn/pdb
• Descriptor: Thioredoxin domain-containing protein, 1,2-ETHANEDIOL, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: tsda, thiol disulfide, structural genomics, center for structural genomics of infectious diseases, csgid, oxidoreductase
• Biological source: Corynebacterium diphtheriae
• Total number of polymer chains: 1
• Total formula weight: 28213.25

Authors

Osipiuk, J.,Reardon-Robinson, M.,Nguyen, M.T.,Sanchez, B.,Ton-That, H.,Joachimiak, A.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2022-04-11, release date: 2022-04-20, Last modification date: 2024-11-06)

Primary citation

Reardon-Robinson, M.E.,Nguyen, M.T.,Sanchez, B.C.,Osipiuk, J.,Ruckert, C.,Chang, C.,Chen, B.,Nagvekar, R.,Joachimiak, A.,Tauch, A.,Das, A.,Ton-That, H.
A cryptic oxidoreductase safeguards oxidative protein folding in Corynebacterium diphtheriae.
Proc.Natl.Acad.Sci.USA, 120:e2208675120-e2208675120, 2023

PubMed Abstract: In many gram-positive Actinobacteria, including and , the conserved thiol-disulfide oxidoreductase MdbA that catalyzes oxidative folding of exported proteins is essential for bacterial viability by an unidentified mechanism. Intriguingly, in , the deletion of blocks cell growth only at 37 °C but not at 30 °C, suggesting the presence of alternative oxidoreductase enzyme(s). By isolating spontaneous thermotolerant revertants of the mutant at 37 °C, we obtained genetic suppressors, all mapped to a single T-to-G mutation within the promoter region of , causing its elevated expression. Strikingly, increased expression of -via suppressor mutations or a constitutive promoter-rescues the pilus assembly and toxin production defects of this mutant, hence compensating for the loss of . 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 expression is upregulated at nonpermissive temperature (40 °C) in wild-type cells, we posit that TsdA has evolved as a compensatory thiol-disulfide oxidoreductase that safeguards oxidative protein folding in against thermal stress.

PubMed: 36787356
DOI: 10.1073/pnas.2208675120

Experimental method

X-RAY DIFFRACTION (1.45 Å)