In vivo oxidative protein folding can be facilitated by oxidation-reduction cycling
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Cho, Seung-Hyun
Boyd, Dana
Heras, Begona
Eser, Markus
Beckwith, Jon
Riggs, Paul
Martin, Jennifer L
Berkmen, Mehmet
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Abstract
Current dogma dictates that bacterial proteins with misoxidized disulfide bonds are shuffled into correctly oxidized states by DsbC. There are two proposed mechanisms for DsbC activity. The first involves a DsbC-only model of substrate disulfide rearrangement. The second invokes cycles of reduction and oxidation of substrate disulfide bonds by DsbC and DsbA respectively. Here, we addressed whether the second mechanism is important in vivo by identifying whether a periplasmic reductase could complement DsbC. We screened for naturally occurring periplasmic reductases in Bacteroides fragilis, a bacterium chosen because we predicted it encodes reductases and has a reducing periplasm. We found that the B. fragilis periplasmic protein TrxP has a thioredoxin fold with an extended N-terminal region; that it is a very active reductase but a poor isomerase; and that it fully complements dsbC. These results provide direct in vivo evidence that correctly folded protein is achievable via cycles of oxidation and reduction.
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Molecular Microbiology
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75
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1
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Biological sciences
Biochemistry and cell biology not elsewhere classified
Agricultural, veterinary and food sciences
Biomedical and clinical sciences