Abstract
Glutaredoxins (GRXs) can be subdivided into two subfamilies: dithiol GRXs with the CPY/FC active site motif, and monothiol GRXs with the CGFS motif. Both subfamilies share a thioredoxin-fold structure. Some monothiol GRXs exist with a single-Grx domain while others have a thioredoxin-like domain (Trx) and one or more Grx domains in tandem. Most fungi have both dithiol and monothiol GRXs with different subcellular locations. GRX-like molecules also exist in fungi that differ by one residue from one of the canonical active site motifs. Additionally, Omega-class glutathione transferases (GSTs) are active as GRXs. Among fungi, the GRXs more extensively studied are those from Saccharomyces cerevisiae. This organism contains two dithiol GRXs (ScGrx1 and ScGrx2) with partially overlapping functions in defence against oxidative stress. In this function, they cooperate with GSTs Gtt1 and Gtt2. While ScGrx1 is cytosolic, two pools exist for ScGrx2, a major one at the cytosol and a minor one at mitochondria. On the other hand, S. cerevisiae cells have two monothiol GRXs with the Trx–Grx structure (ScGrx3 and ScGrx4) that locate at the nucleus and probably regulate the activity of transcription factors such as Aft1, and one monothiol GRX with the Grx structure (ScGrx5) that localizes at the mitochondrial matrix, where it participates in the synthesis of iron–sulphur clusters. The function of yeast Grx5 seems to be conserved along the evolutionary scale.
Similar content being viewed by others
Abbreviations
- CDNB:
-
1-chloro-2,4-dinitrobenzene
- GRX:
-
glutaredoxin
- GSH:
-
reduced glutathione
- HEDS:
-
β-hydroxyethyl disulphide
References
Alves R, Herrero E, Sorribas A (2004) Predictive reconstruction of the mitochondrial iron-sulfur cluster assembly metabolism II. Role of glutaredoxin Grx5. Proteins 57:481–492
Armstrong RN (1997) Structure, catalytic mechanism, and evolution of the glutathione transferases. Chem Res Toxicol 10:2–18
Avery AM, Avery SV (2001) Saccharomyces cerevisiae expresses three phospholipids hydroperoxide glutathione peroxidases. J Biol Chem 276:33730–33735
Bellí G, Polaina J, Tamarit J, de la Torre MA, Rodríguez-Manzaneque MT, Ros J, Herrero E (2002) Structure-function analysis of yeast Grx5 monothiol glutaredoxin defines essential amino acids for the function of the protein. J Biol Chem 277:37590–37596
Belli G, Molina MM, Garcia-Martinez J, Perez-Ortin JE, Herrero E (2004) Saccharomyces cerevisiae glutaredoxin 5-deficient cells subjected to continuous oxidizing conditions are affected in the expression of specific sets of genes. J Biol Chem 279:12386–12395
Bendtsen JD, Nielsen H, von Heijne G, Brunak S (2004) Improved prediction of signal peptides: SignalP 3.0. J Mol Biol 340:783–795
Blaiseau PL, Lesuisse E, Camadro JM (2001) Aft2p, a novel iron-regulated transcription activator that modulates, with Aft1p, intracellular iron use and resistance to oxidative stress in yeast. J Biol Chem 276:34221–34226
Board PG., Coggan M, Chelvanagayam G, Easteal S, Jermiin LS, Schulte GK, Danley DE, Hoth LR, Griffor MC, Kamath AV, Rosner MH, Chrunyk BA, Perregaux DE, Gabel CA, Geoghegan KF, Pandit J (2000) Identification, characterization, and crystal structure of the omega class glutathione transferases. J Biol Chem 275:24798–24806
Bushweller JH, Aslund F, Wurthrich K, Holmgren A (1992) Structural and functional characterization of the mutant Escherichia coli glutaredoxin (C14-S) and its mixed disulfide with glutathione. Biochemistry 31:9288–9293
Carmel-Harel O, Storz G (2000) Roles of the glutathione- and thioredoxin-dependent reduction systems in the Escherichia coli and Saccharomyces cerevisiae responses to oxidative stress. Annu Rev Microbiol 54:439–461
Cho YW, Kim HG, Park EH, Fuchs JA, Lim CJ (2000) Cloning, expression and regulation of Schizosaccharomyces pombe gene encoding thioltransferase. Biochem Biophys Acta 1517:171–175
Choi JH, Lou W, Vancura A (1998) A novel membrane-bound glutathione S-transferase functions in the stationary phase of the yeast Saccharomyces cerevisiae. J Biol Chem 273:29915–29922
Chung WH, Kim KD, Cho YJ, Roe JH (2004) Differential expression and role of two dithiol glutaredoxins Grx1 and Grx2 in Schizosaccharomyces pombe. Biochem Biophys Res Commun 321:922–929
Chung WH, Kim KD, Cho YJ, Roe JH (2005) Localization and function of three monothiol glutaredoxins in Schizosaccharomyces pombe. Biochem Biophys Res Commun 330:604–610
Collinson EJ, Wheeler G, Garrido EO, Avery AM, Avery SV, Grant CM (2002) The yeast glutaredoxins are active as glutathione peroxidases. J Biol Chem 277:16712–16717
Collinson EJ, Grant CM (2003) Role of yeast glutaredoxins as glutathione S-transferases. J Biol Chem 278:22492–22497
Deponte M, Becker K, Rahlfs S (2005) Plasmidium falciparum glutaredoxin-like proteins. Biol Chem 386:33–40
Draculic T, Dawes IW, Grant CM (2000) A single glutaredoxin or thioredoxin is essential for viability in the yeast Saccharomyces cerevisiae. Mol Microbiol 36:1167–1174
Drakulic T, Temple MD, Guido R, Jarolim S, Breitenbach M, Attfield PV, Dawes IW (2005) Involvement of oxidative stress response genes in redox homeostasis, the level of reactive oxidative species, and ageing in Saccharomyces cerevisiae. FEMS Yeast Res 5:1215–1228
Dulhunty A, Gage P, Curtis S, Chelvanayagam G, Board P (2001) The glutathione transferase structural family includes a nuclear chloride channel and a ryanodine receptor calcium release channel modulator. J Biol Chem 276:3319–3323
Fernandes AP, Holmgren A (2004) Glutaredoxins: glutathione-dependent redox enzymes with function as far beyond a␣simple thioredoxin backup system. Antioxid Red Sign 6:63–74
Fernandes AP, Fladvad M, Berndt C, Andresen C, Lillig CH, Neubauer P, Sunnerhagen M, Holmgren A, Vlamis-Gardikas A (2005) A novel monothiol glutaredoxin (Grx4) from Escherichia coli can serve as a substrate for thioredoxin reductase. J Biol Chem 280:24544–24552
Fladvad M, Bellanda M, Fernandes AP, Mammi S, Vlamis-Gardikas A, Holmgren A, Sunnergahen M (2005) Molecular mapping of functionalities in the solution structure of reduced Grx4, a monothiol glutaredoxin from escherichia coli. J Biol Chem 280:24553–24561
Gan ZR, Wells WW (1987) The primary structure of pig liver thioltransferase. J Biol Chem 262:6699–6703
Garcerá A, Barreto L, Piedrafita L, Tamarit J, Herrero E (2006) Saccharomyces cerevisiae cells have three Omega class glutathione transferases acting as 1-Cys thiol transferases. Biochem J doi: 10.1042/BJ20060034
Gasch AP, Spellman PT, Kao CM, Carmel-Harel O, Eisen MB, Storz G, Botstein D, Brown PO (2000) Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell 11:4241–4257
Girardini J, Amirante A, Zemzoumi K, Serra E (2002) Characterization of an omega-class glutathione S-transferase from Schistosoma mansoni with glutaredoxin-like dehydroascorbate reductase and thiol transferase activities. Eur J Biochem 269:5512–5521
Gladyshev VN, Liu A, Novoselov SV, Krysan K, Sun QA, KryukovVM, Kryukov GV, Lou MF (2001) Identification and characterization of a new mammalian glutaredoxin (thioltransferase), Grx2. J Biol Chem 276:30374–30380
Grant CM, Luikenhuis S, Beckhouse A, Soderbergh M, Dawes␣IW (2000) Differential regulation of glutaredoxin gene expression in response to stress conditions in the yeast Saccharomyces cerevisiae. Biochim Biophys Acta 1490:33–42
Hayes JD, Flanagan JU, Jowsey IR (2005) Glutathione transferases. Annu Rev Pharmacol Toxicol 45:51–88
Herrero E, Ros J (2002) Glutaredoxins and oxidative stress defence in yeast. Methods Enzymol 348:136–146
Holmgren A (1989) Thioredoxins and glutaredoxin systems. J Biol Chem 254:13963–13966
Holmgren A, Aslund F (1995) Glutaredoxin. Methods Enzymol 252:283–292
Isakov N, Witte S, Altman A (2000) PICOT-HD: a highly conserved protein domain that is often associated with thioredoxin and glutaredoxin modules. Trends Biochem Sci 25:537–539
Johnson GP, Goebel SJ, Perkus ME, Davis SW, Winslow JP, Paoletti E (1991) Vaccinia virus encodes a protein with similarity to glutaredoxins. Virology 181:378–381
Kim HG, Kim JH, Kim BC, Park EH, Lim CJ (2005a) Carbon source-dependent regulation of a second gene encoding glutaredoxin from the fission yeast Schizosaccharomyces pombe. Mol Biol Rep 32:15–24
Kim HG, Park EH, Lim CJ (2005b) The fission yeast gene encoding monothiol glutaredoxin 5 is regulated by nitrosative and osmotic stresses. Mol Cells 20:43–50
Krogh A, Larsson B, von Heijne G, Sonnhammer ELL (2001) Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol 305:567–580
Laliberte RE, Perregaux DG, Hoth LR, Rosner PJ, Jordan CK, Peese KM, Eggler JF, Dombroski MA, Geoghegan KF, Gabel CA (2003) Glutathione S-transferase omega 1-1 is a target of cytokine release inhibitory drugs and may be responsible for their effect on interleukin-1β posttranslational processing. J Biol Chem 278:16567–16578
Lemaire SD (2004) The glutaredoxin family in oxygenic photosynthetic organisms. Photosynth Res 79:305–318
Lillig CH, Berndt C, Vergnolle O, Lönn ME, Hudemann C, Bill E, Holmgren A (2005) Characterization of human glutaredoxin 2 as iron-sulfur protein: a possible role as redox sensor. Proc Natl Acad Sci USA 102:8168–8173
Lopreiato R, Facchin S, Sartori G, Arrigoni G, Casonato S, Ruzzene M, Pinna LA, Carignani G (2004) Analysis of the interaction between piD261/Bud32, an evolutionary conserved protein kinase of Saccharomyces cerevisiae, and the Grx4 glutaredoxin. Biochem J 377:395–405
Luikenhuis S, Perrone G, Dawes IW, Grant CM (1998) The yeast Saccharomyces cerevisiae contains two glutaredoxin genes that are required for protection against reactive oxygen species. Mol Biol Cell 9:1081–1091
Lundberg M, Johansson C, Chandra J, Enoksson M, Jacobsson G, Ljung J, Johansson M, Holmgren A (2001) Cloning and expression of a novel human glutaredoxin (Grx2) with mitochondrial and nuclear isoforms. J Biol Chem 276:26269–26275
Martin JL (1995) Thioredoxin-a fold for all reasons. Structure 3:245–250
Molina MM, Bellí G, de la Torre MA, Rodríguez-Manzaneque MT, Herrero E (2004) Nuclear monothiol glutaredoxins of Saccharomyces cerevisiae can function as mitochondrial glutaredoxins. J Biol Chem 279:51923–51930
Molina-Navarro MM, Casas C, Piedrafita L, Belli G, Herrero E (2006) Prokaryotic and eukaryotic monothiol glutaredoxins are able to perform the functions of Grx5 in the biogenesis of Fe/S clusters in yeast mitochondria. FEBS Lett 580:2273–2280
Mühlenhoff U, Gerber J, Richhardt N, Lill R (2003) Components involved in assembly and dislocation of iron-sulfur clusters on the scaffold protein Isu1p. EMBO J 22:4815–4825
Mukhopadhyay R, Shi J, Rosen BP (2000) Purification and characterization of Acr2p, the Saccharomyces cerevisiae arsenate reductase. J Biol Chem 275:21149–21157
Nordstrand K, Aslund F, Holmgren A, Otting G, Berndt KD (1999) NMR structure of Escherichia coli glutaredoxin 3-glutathione mixed disulfide complex: implications for the enzymatic mechanism. J Mol Biol 286:541–552
Ojeda L, Keller G, Mühlenhoff U, Rutherford JC, Lill R, Winge DR (2006). Role of glutaredoxin-3 and glutaredoxin-4 in the iron-regulation of the Aft1 transcriptional activator in Saccharomyces cerevisiae. J Biol Chem doi: 10.1074/jbcM602165200
Pedrajas JR, Porras P, Martínez-Galisteo E, Padilla CA, Miranda-Vizuete A, Bárcena JA (2002) Two isoforms of Saccharomyces cerevisiae glutaredoxin 2 are expressed in vivo and localize to different subcellular compartments. Biochem J 364:617–623
Pocsi I, Prado RA, Penninckx MJ (2004) Glutathione, altruistic metabolite in fungi. Adv Microb Physiol 49:1–76
Porras P, Padilla CA, Krayl M, Voos W, Barcena JA (2006) One single in-frame AUG codon is responsible for a diversity of subcellular localizations of glutaredoxin 2 in Saccharomyces cerevisiae. J Biol Chem 281:16551–16562
Rahlfs S, Fischer M, Becker K (2001) Plasmodium falciparum possesses a classical glutaredoxin and a second, glutaredoxin-like protein with a PICOT homology domain. J Biol Chem 276:37133–37140
Rai R, Cooper TG (2005) In vivo specificity of Ure2 protection from heavy metal ion and oxidative cellular damage in Saccharomyces cerevisiae. Yeast 22:343–358
Rodríguez-Manzaneque MT, Ros J, Cabiscol E, Sorribas A, Herrero E (1999) Grx5 glutaredoxin plays a central role in protection against protein oxidative damage in Saccharomyces cerevisiae. Mol Cell Biol 19:8180–8190
Rodríguez-Manzaneque MT, Tamarit J, Bellí G, Ros J, Herrero E (2002) Grx5 is a mitochondrial glutaredoxin required for the activity of iron/sulphur enzymes. Mol Biol Cell 13:1109–1121
Rouhier N, Gelhaye E, Jacquot JP (2004) Plant glutaredoxins: still mysterious systems. Cell Mol Life Sci 61:1266–1277
Rutherford JC, Jaron S, Ray E, Brown PO, Winge DR (2001) A second iron-regulatory system in yeast independent of Aft1p. Proc Natl Acad Sci USA 98:14322–14327
Schmuck EM, Board PG, Whitbread AK, Tetlow N, Blackburn AC, Masoumi A (2005) Characterization of the monomethylarsonate reductase and dehydroascorbate reductase activities of Omega class glutathione transferase 1 for arsenic metabolism and age-at-onset of Alzheimer’s and Parkinson’s diseases. Pharmacogenet Genomics 15:493–501
Sheehan D, Meade G, Foley VM, Dowd CA (2001) Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily. Biochem J 360:1–16
Shenton D, Perrone G, Quinn KA, Dawes IW, Grant CM (2002) Regulation of protein S-thiolation by glutaredoxin 5 in the yeast Saccharomyces cerevisiae. J Biol Chem 277:16853–16859
Sun C, Berardi MJ, Bushweller JH (1998) The NMR solution structure of human glutaredoxin in the fully reduced form. J Mol Biol 280:687–701
Tamarit J, Bellí G, Cabiscol E, Herrero E, Ros J (2003) Biochemical characterization of yeast mitochondrial Grx5 monothiol glutaredoxin. J Biol Chem 278:25745–25751
Teixeira MC, Telo JP, Duarte NF, Sá-Correia I (2004) The herbicide 2,4-dichlorophenoxyacetic acid induces the generation of free-radicals and associated oxidative stress responses in yeast. Biochem Biophys Res Commun 324:1101–1107
Trotter EW, Grant CM (2003) Non-reciprocal regulation of the redox state of the glutathione/glutaredoxin and thioredoxin systems. EMBO Rep 4:184–189
Vilella F, Alves R, Rodríguez-Manzaneque MT, Bellí G, Swaminathan S, Sunnerhagen P, Herrero E (2004) Evolution and cellular function of monothiol glutaredoxins: involvement in iron-sulfur cluster assembly. Comp Funct Genom 5:328–341
Vlamis-Gardikas A, Holmgren A (2002) Thioredoxin and glutaredoxin isoforms. Methods Enzymol 347:286–296
Wheeler GL, Grant CM (2004) Regulation of redox homeostasis␣in the yeast Saccharomyces cerevisiae. Physiol Plant 120:12–20
Whitbread AK, Masoumi A, Tetlow N, Schmuck E, Coggan M, Board PG (2005) Characterization of the Omega-class of glutathione transfrases. Methods Enzymol 401:78–99
Wingert RA, Galloway JL, Barut B, Foott H, Fraenkel P, Axe JL, Weber GJ,Dooley K, Davidson AJ, Schmid B, Paw BH, Shaw GC, Kingsley P, Palis J, Schubert H, Chen O, Kaplan J, Zon LI, Tubingen 2000 Screen Consortium (2005) Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis. Nature 436:1035–1039
Witte S, Villalba M, Bi K, Liu Y, Isakov N, Altman A (2000) Inhibition of the c-Jun N-terminal kinase/AP-1 and NF-kappaB pathways by PICOT, a novel protein kinase C-interacting protein with a thioredoxin homology domain. J Biol Chem 275:1902–1909
Xia TH, Bushweller JH, Sodano P, Billeter M, Bjornberg O, Holmgren A, Wuthrich K (1992) NMR structure of oxidized Escherichia coli glutaredoxin: comparison with reduced E. coli glutaredoxin and functionally related proteins. Protein Sci 1:310–321
Yamaguchi-Iwai Y, Dancis A, Klausner RD (1995) AFT1: a mediator of iron regulated transcriptional control in Saccharomyces cerevisiae. EMBO J 14:1231–1239
Acknowledgements
Work carried out in the laboratories of the authors was supported by the Ministerio de Educación y Ciencia, Spain (BFU2004-03167/BMC and BFU2004-00593/BMC) and Generalitat de Catalunya (2005SGR00677).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Herrero, E., Ros, J., Tamarit, J. et al. Glutaredoxins in fungi. Photosynth Res 89, 127–140 (2006). https://doi.org/10.1007/s11120-006-9079-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11120-006-9079-3