Selenoprotein K form an intermolecular diselenide bond with unusually high redox potential

FEBS Lett. 2014 Sep 17;588(18):3311-21. doi: 10.1016/j.febslet.2014.07.037. Epub 2014 Aug 10.

Abstract

Selenoprotein K (SelK) is a membrane protein involved in antioxidant defense, calcium regulation and the ER-associated protein degradation pathway. We found that SelK exhibits a peroxidase activity with a rate that is low but within the range of other peroxidases. Notably, SelK reduced hydrophobic substrates, such as phospholipid hydroperoxides, which damage membranes. Thus, SelK might be involved in membrane repair or related pathways. SelK was also found to contain a diselenide bond-the first intramolecular bond of that kind reported for a selenoprotein. The redox potential of SelK was -257 mV, significantly higher than that of diselenide bonds in small molecules or proteins. Consequently, SelK can be reduced by thioredoxin reductase. These finding are essential for understanding SelK activity and function.

Keywords: Diselenide bond; Peroxidase; Phospholipid hydroperoxide; Selenocysteine; Selenoprotein K.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Glutaredoxins / chemistry
  • Glutathione Reductase / chemistry
  • Humans
  • Kinetics
  • Lipid Peroxides / chemistry
  • NADP / chemistry
  • Oxidation-Reduction
  • Selenium Compounds / chemistry*
  • Selenoproteins / chemistry*
  • Substrate Specificity
  • Thioredoxin-Disulfide Reductase / chemistry
  • Thioredoxins / chemistry

Substances

  • Glutaredoxins
  • Lipid Peroxides
  • Selenium Compounds
  • Selenoproteins
  • selenoprotein K, human
  • Thioredoxins
  • NADP
  • Glutathione Reductase
  • Thioredoxin-Disulfide Reductase