Grx5 Glutaredoxin Plays a Central Role in Protection against Protein Oxidative Damage in Saccharomyces cerevisiae
Open Access
- 1 December 1999
- journal article
- research article
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 19 (12), 8180-8190
- https://doi.org/10.1128/mcb.19.12.8180
Abstract
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 grx5cells, 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 ofgrx5 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.Keywords
This publication has 67 references indexed in Scilit:
- Bridge over Troubled WatersCell, 1999
- Recent Trends in Glutathione Biochemistry—Glutathione–Protein Interactions: A Molecular Link between Oxidative Stress and Cell Proliferation?Biochemical and Biophysical Research Communications, 1998
- Cloning, Overexpression, and Characterization of Glutaredoxin 2, An Atypical Glutaredoxin from Escherichia coliJournal of Biological Chemistry, 1997
- Yeast glutathione reductase is required for protection against oxidative stress and is a target gene for yAP‐1 transcriptional regulationMolecular Microbiology, 1996
- The role of the YAP1 and YAP2 genes in the regulation of the adaptive oxidative stress responses of Saccharomyces cerevisiaeMolecular Microbiology, 1995
- A method to predict functional residues in proteinsNature Structural & Molecular Biology, 1995
- New heterologous modules for classical or PCR‐based gene disruptions in Saccharomyces cerevisiaeYeast, 1994
- Differential susceptibility of plasma proteins to oxidative modification: Examination by western blot immunoassayFree Radical Biology & Medicine, 1994
- Cloning and sequencing of a gene encoding yeast thioltransferaseBiochemical and Biophysical Research Communications, 1992
- Structural and functional characterization of the mutant Escherichia coli glutaredoxin (C14.fwdarw.S) and its mixed disulfide with glutathioneBiochemistry, 1992