Mammalian selenoprotein thioredoxin-glutathione reductase. Roles in disulfide bond formation and sperm maturation.
Thioredoxin reductases (TRs) are important redox regulatory enzymes, which control the redox state of thioredoxins. Mammals have cytosolic and mitochondrial TRs, which contain an essential selenocysteine residue and reduce cytosolic and mitochondrial thioredoxins. In addition, thioredoxin/glutathione reductase (TGR) was identified, which is a fusion of an N-terminal glutaredoxin domain and the TR module. Here we show that TGR is expressed at low levels in various tissues but accumulates in testes after puberty. The protein is particularly abundant in elongating spermatids at the site of mitochondrial sheath formation but is absent in mature sperm. We found that TGR can catalyze isomerization of protein and interprotein disulfide bonds and localized this function to its thiol domain. TGR targets include proteins that form structural components of the sperm, including glutathione peroxidase GPx4/PHGPx. Together, TGR and GPx4 can serve as a novel disulfide bond formation system. Both enzymes contain a catalytic selenocysteine consistent with the role of selenium in male reproduction.
Su
Dan
D
Department of Biochemistry, University of Nebraska, Lincoln, Nebraska 68588, USA.
Novoselov
Sergey V
SV
Sun
Qi-An
QA
Moustafa
Mohamed E
ME
Zhou
You
Y
Oko
Richard
R
Hatfield
Dolph L
DL
Gladyshev
Vadim N
VN
D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism / Q000502:physiology*; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D010544:Peroxidases / Q000737:chemistry; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry; D051140:Selenoproteins; D013079:Sperm Maturation; D013094:Spermatozoa / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D014018:Tissue Distribution
D003432:Cross-Linking Reagents; D004220:Disulfides; D009097:Multienzyme Complexes; D011506:Proteins; D011994:Recombinant Proteins; D051140:Selenoproteins; D010544:Peroxidases; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; D009247:NADH, NADPH Oxidoreductases; C466433:thioredoxin glutathione reductase