NMR structures of the selenoproteins Sep15 and SelM reveal redox activity of a new thioredoxin-like family.
Selenium has significant health benefits, including potent cancer prevention activity and roles in immune function and the male reproductive system. Selenium-containing proteins, which incorporate this essential micronutrient as selenocysteine, are proposed to mediate the positive effects of dietary selenium. Presented here are the solution NMR structures of the selenoprotein SelM and an ortholog of the selenoprotein Sep15. These data reveal that Sep15 and SelM are structural homologs that establish a new thioredoxin-like protein family. The location of the active-site redox motifs within the fold together with the observed localized conformational changes after thiol-disulfide exchange and measured redox potential indicate that they have redox activity. In mammals, Sep15 expression is regulated by dietary selenium, and either decreased or increased expression of this selenoprotein alters redox homeostasis. A physiological role for Sep15 and SelM as thiol-disulfide oxidoreductases and their contribution to the quality control pathways of the endoplasmic reticulum are discussed.
Ferguson
Andrew D
AD
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Labunskyy
Vyacheslav M
VM
Fomenko
Dmitri E
DE
Araç
Demet
D
Chelliah
Yogarany
Y
Amezcua
Carlos A
CA
Rizo
Josep
J
Gladyshev
Vadim N
VN
Deisenhofer
Johann
J
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002470:Cell Survival; D029721:Drosophila Proteins / Q000737:chemistry*; D004331:Drosophila melanogaster; D004926:Escherichia coli / Q000378:metabolism; D019476:Insect Proteins / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011487:Protein Conformation; D034622:RNA Interference; D011994:Recombinant Proteins / Q000737:chemistry; D012643:Selenium / Q000494:pharmacology; D017279:Selenocysteine / Q000737:chemistry; D051140:Selenoproteins / Q000737:chemistry*; D013438:Sulfhydryl Compounds; D013879:Thioredoxins / Q000737:chemistry*
C509351:CG7484 protein, Drosophila; D029721:Drosophila Proteins; D019476:Insect Proteins; D011994:Recombinant Proteins; C495239:Selenof protein, mouse; D051140:Selenoproteins; C499178:Sepm protein, mouse; D013438:Sulfhydryl Compounds; D017279:Selenocysteine; D013879:Thioredoxins; D012643:Selenium