Metal-binding properties of selenoprotein P—its relation to structure and function

Abstract

Selenoprotein P (SeP), encoded by the SELENOP gene, is the major selenium-containing protein in human plasma. SeP has 10 residues of selenocysteine (Sec, cysteine analog in which the sulfur is replaced by selenium), and Sec plays a significant role in the multifunctional properties of SeP. The one Sec residue on the N-terminal side functions for the redox reaction that reduces lipid hydroperoxides, while the 9 Sec residues on the C-terminal side are responsible for the selenium supplying activity. In the middle of SeP, the domain rich in basic amino acids containing consecutive histidine is present. SeP has been reported to have multiple metal-binding abilities such as Hg, Cd, Cu, Ni, Zn, and Co; however, its physiological significance and the effects on SeP functions remain unclear. In this review, the findings to date on the metal-binding properties of SeP and its structural relevance are summarized, particularly for methylmercury. The binding of other selenoproteins to metals is also described. Finally, the interactions of selenoproteins with various metals and its significance for biological defense are discussed.