NMR structures of the selenoproteins Sep15 and SelM reveal redox activity of a new thioredoxin-like family

Andrew D. Ferguson, Vyacheslav M. Labunskyy, Dmitri E. Fomenko, Demet Araç, Yogarany Chelliah, Carlos A. Amezcua, Jose Rizo-Rey, Vadim N. Gladyshev, Johann Deisenhofer

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)3536-3543
Number of pages8
JournalJournal of Biological Chemistry
Volume281
Issue number6
DOIs
StatePublished - Feb 10 2006

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Selenoproteins
Thioredoxins
Selenium
Oxidation-Reduction
Nuclear magnetic resonance
Protein Disulfide Reductase (Glutathione)
Selenocysteine
Mammals
Micronutrients
Insurance Benefits
Sulfhydryl Compounds
Endoplasmic Reticulum
Disulfides
Quality Control
Quality control
Catalytic Domain
Proteins
Homeostasis
Health
Neoplasms

ASJC Scopus subject areas

  • Biochemistry

Cite this

NMR structures of the selenoproteins Sep15 and SelM reveal redox activity of a new thioredoxin-like family. / Ferguson, Andrew D.; Labunskyy, Vyacheslav M.; Fomenko, Dmitri E.; Araç, Demet; Chelliah, Yogarany; Amezcua, Carlos A.; Rizo-Rey, Jose; Gladyshev, Vadim N.; Deisenhofer, Johann.

In: Journal of Biological Chemistry, Vol. 281, No. 6, 10.02.2006, p. 3536-3543.

Research output: Contribution to journalArticle

Ferguson, Andrew D. ; Labunskyy, Vyacheslav M. ; Fomenko, Dmitri E. ; Araç, Demet ; Chelliah, Yogarany ; Amezcua, Carlos A. ; Rizo-Rey, Jose ; Gladyshev, Vadim N. ; Deisenhofer, Johann. / NMR structures of the selenoproteins Sep15 and SelM reveal redox activity of a new thioredoxin-like family. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 6. pp. 3536-3543.
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AU - Araç, Demet

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AB - 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.

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