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ATP-dependent reduction of cysteine–sulphinic acid by S. cerevisiae sulphiredoxin

Nature volume 425, pages 980–984 (2003)Cite this article

Abstract

Proteins contain thiol-bearing cysteine residues that are sensitive to oxidation, and this may interfere with biological function either as ‘damage’ or in the context of oxidant-dependent signal transduction. Cysteine thiols oxidized to sulphenic acid are generally unstable, either forming a disulphide with a nearby thiol or being further oxidized to a stable sulphinic acid1,2. Cysteine–sulphenic acids and disulphides are known to be reduced by glutathione or thioredoxin in biological systems, but cysteine–sulphinic acid derivatives have been viewed as irreversible protein modifications. Here we identify a yeast protein of relative molecular mass Mr = 13,000, which we have named sulphiredoxin (identified by the US spelling ‘sulfiredoxin’, in the Saccharomyces Genome Database), that is conserved in higher eukaryotes and reduces cysteine–sulphinic acid in the yeast peroxiredoxin Tsa1. Peroxiredoxins are ubiquitous thiol-containing antioxidants that reduce hydroperoxides3,4,5 and control hydroperoxide-mediated signalling in mammals6,7,8. The reduction reaction catalysed by sulphiredoxin requires ATP hydrolysis and magnesium, involving a conserved active-site cysteine residue which forms a transient disulphide linkage with Tsa1. We propose that reduction of cysteine–sulphinic acids by sulphiredoxin involves activation by phosphorylation followed by a thiol-mediated reduction step. Sulphiredoxin is important for the antioxidant function of peroxiredoxins, and is likely to be involved in the repair of proteins containing cysteine–sulphinic acid modifications, and in signalling pathways involving protein oxidation.

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Figure 1: Srx1, a member of a new eukaryotic protein family, is induced by H2O2 and contributes to H2O2 resistance.
Figure 2: Srx1 is associated to Prxs non-covalently and by DTT-sensitive linkages.
Figure 3: Srx1-dependent recycling of the Tsa1 cysteine–sulphinic acid form in vivo.
Figure 4: ATP-dependent reduction of the cysteine–sulphinic acid of Tsa1 by Srx1 in vitro.

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Acknowledgements

We thank G. Clement for mass spectrometry analysis, M.-B. Barrault for technical assistance, G. Lagniel for 2D-PAGE analysis, J. Acker and C. Ducrot for baculovirus protein expression, and I. Artaud and B. Rousseau for suggestions on the chemistry of sulphur. Many thanks to T. Rabilloud for sharing unpublished results, to A. Sentenac, A. Delaunay, G. Rousselet, F. Tacnet, S. Desaint, and S. Le Maout for discussion and comments on the manuscript and A. Sentenac for his support. This work was supported by grant from ARC to M.B.T. and a CFR CEA fellowship to B.B.

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  1. Laboratoire Stress Oxydants et Cancer, SBGM, DBJC, CEA-Saclay, Gif-sur-Yvette cedex, 91191, France

    Benoît Biteau & Michel B. Toledano

  2. Laboratoire de Physiogénomique, SBGM, DBJC, CEA-Saclay, Gif-sur-Yvette cedex, 91191, France

    Jean Labarre

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Correspondence to Michel B. Toledano.

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Biteau, B., Labarre, J. & Toledano, M. ATP-dependent reduction of cysteine–sulphinic acid by S. cerevisiae sulphiredoxin. Nature 425, 980–984 (2003). https://doi.org/10.1038/nature02075

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