Graded Response of the Multifunctional 2-Cysteine Peroxiredoxin, CgPrx, to Increasing Levels of Hydrogen Peroxide in Corynebacterium glutamicum.
Eukaryotic typical 2-cysteine (Cys) peroxiredoxins (Prxs) are multifunctional proteins subjected to complex regulation and play important roles in oxidative stress resistance, hydrogen peroxide (H2O2) signaling modulation, aging, and cancer, but the information on the biochemical functions and regulation mechanisms of prokaryotic atypical 2-Cys Prxs is largely lacking.



In this study, we show that at low peroxide concentrations, the atypical 2-Cys Prx in Corynebacterium glutamicum (CgPrx) mainly exists as monomers and displays thioredoxin (Trx)-dependent peroxidase activity. Moderate oxidative stress causes reversible S-mycothiolation of the H2O2-sensing Cys63 residue, which keeps CgPrx exclusively in dimer form with neither peroxidase nor chaperone activity. Then, the increased levels of H2O2could act as a messenger to oxidize the redox-sensitive regulator hydrogen peroxide-inducible gene activator, leading to activation of expression of the more efficient mycothiol peroxidase and catalase to eliminate excessive peroxide. If oxidative stress is too severe, the H2O2-sensing Cys63 becomes hyperoxidized to sulfonic acid, which irreversibly inactivates the peroxidase activity, and most of CgPrx will be converted to multimeric chaperones for salvage of damaged proteins.



We demonstrate for the first time that atypical 2-Cys CgPrx acts as both a Trx-dependent peroxidase and a molecular chaperone and plays a regulatory role in modulating the peroxide-mediated signaling cascades.



These results reveal that CgPrx functions as a multifunctional protein crucial for adapting appropriate responses to different levels of oxidative challenge in C. glutamicum. Antioxid. Redox Signal. 26, 1-14.
1 State Key Laboratory of Crop Stress Biology for Arid Areas and College of Life Sciences, Northwest A&F University , Yangling, China .|2 College of Plant Protection, Northwest A&F University , Yangling, China .
Meiru
M
Si
1 State Key Laboratory of Crop Stress Biology for Arid Areas and College of Life Sciences, Northwest A&F University , Yangling, China .
Tietao
T
Wang
1 State Key Laboratory of Crop Stress Biology for Arid Areas and College of Life Sciences, Northwest A&F University , Yangling, China .
Junfeng
J
Pan
1 State Key Laboratory of Crop Stress Biology for Arid Areas and College of Life Sciences, Northwest A&F University , Yangling, China .
Jinshui
J
Lin
1 State Key Laboratory of Crop Stress Biology for Arid Areas and College of Life Sciences, Northwest A&F University , Yangling, China .
Can
C
Chen
1 State Key Laboratory of Crop Stress Biology for Arid Areas and College of Life Sciences, Northwest A&F University , Yangling, China .
Yahong
Y
Wei
2 College of Plant Protection, Northwest A&F University , Yangling, China .
Zhiqiang
Z
Lu
1 State Key Laboratory of Crop Stress Biology for Arid Areas and College of Life Sciences, Northwest A&F University , Yangling, China .
Gehong
G
Wei
1 State Key Laboratory of Crop Stress Biology for Arid Areas and College of Life Sciences, Northwest A&F University , Yangling, China .
Xihui
X
Shen
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002384:Catalysis; D048230:Corynebacterium glutamicum / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D018832:Molecular Chaperones / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D054464:Peroxiredoxins / Q000737:chemistry / Q000378:metabolism*; D055503:Protein Multimerization / Q000187:drug effects; D015398:Signal Transduction
D001426:Bacterial Proteins; D004220:Disulfides; D018832:Molecular Chaperones; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins; D009195:Peroxidase; D003545:Cysteine
Corynebacterium glutamicum; S-mycothiolation; molecular chaperone; mycothiol; peroxiredoxin