Glutathione- and glutaredoxin-dependent reduction of methionine sulfoxide reductase A

• Published in: FEBS letters Vol. 586; no. 21; pp. 3894 - 3899
• Main Authors: Couturier, Jérémy, Vignols, Florence, Jacquot, Jean-Pierre, Rouhier, Nicolas
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 02.11.2012; Wiley
• Subjects: Amino Acid Sequence; Biological Evolution; Escherichia coli; Genetic Complementation Test; Glutaredoxin; Glutaredoxins - genetics; Glutaredoxins - metabolism; Glutathione; Glutathione - metabolism; Gracilaria - enzymology; Gracilaria - genetics; Gracilaria gracilis; Grx; GSH; Kinetics; Life Sciences; Methionine - analogs & derivatives; Methionine - metabolism; methionine sufoxide; Methionine sufoxide reductase; methionine sulfoxide reductase; Methionine Sulfoxide Reductases - genetics; Methionine Sulfoxide Reductases - metabolism; MetO; Molecular Sequence Data; Msr; Mutant Chimeric Proteins - genetics; Mutant Chimeric Proteins - metabolism; Oxidation-Reduction; Populus - enzymology; Populus - genetics; Recombinant Proteins; Saccharomyces cerevisiae; Sequence Alignment; thioredoxin; Trx; Methionine sufoxide reductase; MetO; Glutaredoxin; Trx; Grx; GSH; Msr; Glutathione; Gracilaria gracilis
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2012.09.020

► A Grx-Grx-MsrA fusion catalyzes the glutathione-dependent reduction of MetO. ► Plant-type MsrAs are recycled both by thioredoxins and glutaredoxins. ► A catalytic mechanism for the Grx-dependent regeneration of 3-Cys MsrA is proposed. ► Natural hybrid proteins help identifying protein interactions in other organisms. A natural fusion occurring between two tandemly repeated glutaredoxin (Grx) modules and a methionine sulfoxide reductase A (MsrA) has been detected in Gracilaria gracilis. Using an in vivo yeast complementation assay and in vitro activity measurements, we demonstrated that this fusion enzyme was able to reduce methionine sulfoxide into methionine using glutathione as a reductant. Consistently, a poplar cytosolic MsrA can be regenerated in vitro by glutaredoxins with an efficiency comparable to that of thioredoxins, but using a different mechanism. We hypothesize that the glutathione/glutaredoxin system could constitute an evolutionary conserved alternative regeneration system for MsrA.