NMR Structures of the Selenoproteins Sep15 and SelM Reveal Redox Activity of a New Thioredoxin-like Family*
- Andrew D. Ferguson‡,1,
- Vyacheslav M. Labunskyy§,
- Dmitri E. Fomenko§,
- Demet Ara燶,
- Yogarany Chelliah∥,
- Carlos A. Amezcua‡,
- Josep Rizo‡¶,
- Vadim N. Gladyshev§ and
- Johann Deisenhofer‡∥,2
- ∥Howard Hughes Medical Institute, and the ‡Department of Biochemistry and ¶Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, and the §Department of Biochemistry, University of Nebraska, Lincoln, Nebraska 68588
- ↵2 An investigator with the Howard Hughes Medical Institute. To whom correspondence should be addressed: Dept. of Biochemistry, University of Texas Southwestern Medical Center at Dallas, TX 75390. Tel.: 214-645-5941; Fax: 214-645-5939; E-mail: Johann.Deisenhofer{at}utsouthwestern.edu.
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.
- Received October 20, 2005.
- Revision received November 23, 2005.
- The American Society for Biochemistry and Molecular Biology, Inc.
