A cryptic oxidoreductase safeguards oxidative protein folding in Corynebacterium diphtheriae
Reardon-Robinson ME, Nguyen MT, Sanchez BC, Osipiuk J, Rückert C, Chang C, Chen B, Nagvekar R, Joachimiak A, Tauch A, Das A, et al. (2023)
Proceedings of the National Academy of Sciences of the United States of America 120(8): e2208675120.
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Autor*in
Reardon-Robinson, Melissa E;
Nguyen, Minh Tan;
Sanchez, Belkys C;
Osipiuk, Jerzy;
Rückert, ChristianUniBi
;
Chang, Chungyu;
Chen, Bo;
Nagvekar, Rahul;
Joachimiak, Andrzej;
Tauch, AndreasUniBi;
Das, Asis;
Ton-That, Hung
Alle
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Alle
Einrichtung
Abstract / Bemerkung
In 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 °C but not at 30 °C, suggesting the presence of alternative oxidoreductase enzyme(s). By isolating spontaneous thermotolerant revertants of the mdbA mutant at 37 °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 °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.
Erscheinungsjahr
2023
Zeitschriftentitel
Proceedings of the National Academy of Sciences of the United States of America
Band
120
Ausgabe
8
Art.-Nr.
e2208675120
eISSN
1091-6490
Page URI
https://pub.uni-bielefeld.de/record/2969067
Zitieren
Reardon-Robinson ME, Nguyen MT, Sanchez BC, et al. A cryptic oxidoreductase safeguards oxidative protein folding in Corynebacterium diphtheriae. Proceedings of the National Academy of Sciences of the United States of America. 2023;120(8): e2208675120.
Reardon-Robinson, M. E., Nguyen, M. T., Sanchez, B. C., Osipiuk, J., Rückert, C., Chang, C., Chen, B., et al. (2023). A cryptic oxidoreductase safeguards oxidative protein folding in Corynebacterium diphtheriae. Proceedings of the National Academy of Sciences of the United States of America, 120(8), e2208675120. https://doi.org/10.1073/pnas.2208675120
Reardon-Robinson, Melissa E, Nguyen, Minh Tan, Sanchez, Belkys C, Osipiuk, Jerzy, Rückert, Christian, Chang, Chungyu, Chen, Bo, et al. 2023. “A cryptic oxidoreductase safeguards oxidative protein folding in Corynebacterium diphtheriae”. Proceedings of the National Academy of Sciences of the United States of America 120 (8): e2208675120.
Reardon-Robinson, M. E., Nguyen, M. T., Sanchez, B. C., Osipiuk, J., Rückert, C., Chang, C., Chen, B., Nagvekar, R., Joachimiak, A., Tauch, A., et al. (2023). A cryptic oxidoreductase safeguards oxidative protein folding in Corynebacterium diphtheriae. Proceedings of the National Academy of Sciences of the United States of America 120:e2208675120.
Reardon-Robinson, M.E., et al., 2023. A cryptic oxidoreductase safeguards oxidative protein folding in Corynebacterium diphtheriae. Proceedings of the National Academy of Sciences of the United States of America, 120(8): e2208675120.
M.E. Reardon-Robinson, et al., “A cryptic oxidoreductase safeguards oxidative protein folding in Corynebacterium diphtheriae”, Proceedings of the National Academy of Sciences of the United States of America, vol. 120, 2023, : e2208675120.
Reardon-Robinson, M.E., Nguyen, M.T., Sanchez, B.C., Osipiuk, J., Rückert, 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. Proceedings of the National Academy of Sciences of the United States of America. 120, : e2208675120 (2023).
Reardon-Robinson, Melissa E, Nguyen, Minh Tan, Sanchez, Belkys C, Osipiuk, Jerzy, Rückert, Christian, Chang, Chungyu, Chen, Bo, Nagvekar, Rahul, Joachimiak, Andrzej, Tauch, Andreas, Das, Asis, and Ton-That, Hung. “A cryptic oxidoreductase safeguards oxidative protein folding in Corynebacterium diphtheriae”. Proceedings of the National Academy of Sciences of the United States of America 120.8 (2023): e2208675120.
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