The Intrinsically Disordered Membrane Enzymes Selenoprotein S and Selenoprotein K

Abstract

Selenoproteins constitute a family of enzymes involved in the management and regulation of reactive oxygen species, signaling molecules that are also affiliated with molecular damage and disease. The family contains two intrinsically disordered membrane proteins: selenoprotein S (SelS) and selenoprotein K (SelK). Both of these bitopic membrane proteins reside in the endoplasmic reticulum and contain the highly reactive amino acid selenocysteine, The precise function of SelK and SelS is presently still unknown, however it has been shown that in vivo they participate in anti-oxidant defense. In addition they are members of the Endoplasmic Reticulum Associated Protein Degradation (ERAD) pathway, which is responsible for dislocation of misfolded proteins from the ER for degradation in the cytoplasm. We have shown that SelK and SelS belong to the very small group of intrinsically disordered proteins that exhibit enzymatic functions. We demonstrate that SelS is an efficient reductase capable of reducing disulfide bonds, while SelK has a weak but nevertheless relevant lipid peroxidase activity. The latter is particular noteworthy because lipid hydroperoxides are accessible to only a limited set of peroxidases, but play a critical role in membrane health.