Glutathionylation induces the dissociation of 1-Cys D-peroxiredoxin non-covalent homodimer.
1-Cys peroxiredoxins (1-Cys Prxs) are antioxidant enzymes that catalyze the reduction of hydroperoxides into alcohols using a strictly conserved cysteine. 1-Cys B-Prxs, homologous to human PrxVI, were recently shown to be reactivated by glutathione S-transferase (GST) pi via the formation of a GST-Prx heterodimer and Prx glutathionylation. In contrast, 1-Cys D-Prxs, homologous to human PrxV, are reactivated by the glutaredoxin-glutathione system through an unknown mechanism. To investigate the mechanistic events that mediate the 1-Cys D-Prx regeneration, interaction of the Prx with glutathione was studied by mass spectrometry and NMR. This work reveals that the Prx can be glutathionylated on its active site cysteine. Evidences are reported that the glutathionylation of 1-Cys D-Prx induces the dissociation of the Prx non-covalent homodimer, which can be recovered by reduction with dithiothreitol. This work demonstrates for the first time the existence of a redox-dependent dimer-monomer switch in the Prx family, similar to the decamer-dimer switch for the 2-Cys Prxs.
Noguera-Mazon
Valérie
V
CNRS, Unité Mixte de Recherche, 5180 Sciences Analytiques,Ecole Supérieure Chimie PhysiqueElectronique de Lyon, Domaine Scientifique de la Doua, Université Claude Bernard, Lyon1, 69622 Villeurbanne, France.
Lemoine
Jérôme
J
Walker
Olivier
O
Rouhier
Nicolas
N
Salvador
Arnaud
A
Jacquot
Jean-Pierre
JP
Lancelin
Jean-Marc
JM
Krimm
Isabelle
I
D001665:Binding Sites; D003545:Cysteine / Q000737:chemistry; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D004229:Dithiothreitol / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000737:chemistry*; D054464:Peroxiredoxins; D032107:Populus; D011485:Protein Binding
D004220:Disulfides; D010544:Peroxidases; D054464:Peroxiredoxins; D005982:Glutathione Transferase; D005978:Glutathione; D003545:Cysteine; D004229:Dithiothreitol