Grx5 glutaredoxin plays a central role in protection against protein oxidative damage in Saccharomyces cerevisiae.
Glutaredoxins are members of a superfamily of thiol disulfide oxidoreductases involved in maintaining the redox state of target proteins. In Saccharomyces cerevisiae, two glutaredoxins (Grx1 and Grx2) containing a cysteine pair at the active site had been characterized as protecting yeast cells against oxidative damage. In this work, another subfamily of yeast glutaredoxins (Grx3, Grx4, and Grx5) that differs from the first in containing a single cysteine residue at the putative active site is described. This trait is also characteristic for a number of glutaredoxins from bacteria to humans, with which the Grx3/4/5 group has extensive homology over two regions. Mutants lacking Grx5 are partially deficient in growth in rich and minimal media and also highly sensitive to oxidative damage caused by menadione and hydrogen peroxide. A significant increase in total protein carbonyl content is constitutively observed in grx5 cells, and a number of specific proteins, including transketolase, appear to be highly oxidized in this mutant. The synthetic lethality of the grx5 and grx2 mutations on one hand and of grx5 with the grx3 grx4 combination on the other points to a complex functional relationship among yeast glutaredoxins, with Grx5 playing a specially important role in protection against oxidative stress both during ordinary growth conditions and after externally induced damage. Grx5-deficient mutants are also sensitive to osmotic stress, which indicates a relationship between the two types of stress in yeast cells.
Rodríguez-Manzaneque
M T
MT
Departament de Ciències Mèdiques Bàsiques, Facultat de Medicina, Universitat de Lleida, 25198 Lleida, Spain.
Ros
J
J
Cabiscol
E
E
Sorribas
A
A
Herrero
E
E
D000595:Amino Acid Sequence; D000818:Animals; D015870:Gene Expression; D054477:Glutaredoxins; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009995:Osmosis; D018384:Oxidative Stress; D010088:Oxidoreductases; D011490:Protein Disulfide Reductase (Glutathione) / Q000235:genetics / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid
C516008:GLRX2 protein, human; D054477:Glutaredoxins; C516012:Grx4 protein, S cerevisiae; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D010088:Oxidoreductases; D011490:Protein Disulfide Reductase (Glutathione)