A novel group of glutaredoxins in the cis-Golgi critical for oxidative stress resistance.
Glutaredoxins represent a ubiquitous family of proteins that catalyze the reduction of disulfide bonds in their substrate proteins by use of reduced glutathione. In an attempt to identify the full complement of glutaredoxins in baker's yeast, we found three so-far uncharacterized glutaredoxin-like proteins that we named Grx6, Grx7, and Grx8. Grx6 and Grx7 represent closely related monothiol glutaredoxins that are synthesized with N-terminal signal sequences. Both proteins are located in the cis-Golgi, thereby representing the first glutaredoxins found in a compartment of the secretory pathway. In contrast to formerly described monothiol glutaredoxins, Grx6 and Grx7, showed a high glutaredoxin activity in vitro. Grx6 and Grx7 overlap in their activity and deletion mutants lacking both proteins show growth defects and a strongly increased sensitivity toward oxidizing agents such as hydrogen peroxide or diamide. Our observations suggest that Grx6 and Grx7 do not play a general role in the oxidative folding of proteins in the early secretory pathway but rather counteract the oxidation of specific thiol groups in substrate proteins.
Mesecke
Nikola
N
Institute of Physiological Chemistry, University of Munich, 81377 Munich, Germany.
Spang
Anne
A
Deponte
Marcel
M
Herrmann
Johannes M
JM
D002458:Cell Fractionation; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D054477:Glutaredoxins / Q000737:chemistry / Q000378:metabolism*; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012995:Solubility / Q000187:drug effects
C532450:GRX7 protein, S cerevisiae; C000588987:GRX8 protein, S cerevisiae; D054477:Glutaredoxins; C527470:Grx6 protein, S cerevisiae; D016877:Oxidants; D029701:Saccharomyces cerevisiae Proteins