The selenium content of SEPP1 versus selenium requirements in vertebrates

Abstract

Selenoprotein P (SEPP1) distributes selenium (Se) throughout the body via the circulatory system. For vertebrates, the Se content of SEPP1 varies from 7 to 18 Se atoms depending on the species, but the reason for this variation remains unclear. Herein we provide evidence that vertebrate SEPP1 Sec content correlates positively with Se requirements. As the Se content of full length SEPP1 is genetically determined, this presents a unique case where a nutrient requirement can be predicted based on genomic sequence information.

Keywords: Nutrition; SEPP1; Selenium requirements; Selenoprotein; Selenoprotein P.

Figure 1. The receptor binding sites and selenocysteine (Sec) residues of vertebrate selenoprotein P (SEPP1).

From the N-terminal side, SEPP1 is comprised of a conserved N-terminal domain Sec residue, followed by several proposed heparin binding sites which include a histidine rich region. Following this, there is the shorter Sec residue rich C-terminal domain which contains an APOER2 binding site. The C-terminal domain can be further divided into two subdomains. The first subdomain exists on the N-terminal side of the APOER2 binding site and contains a region with a low conservation of Sec residues among vertebrates (mainly due to Sec to cysteine (Cys) conversions (Lobanov, Hatfield & Gladyshev, 2008)). The second subdomain is located downstream of the APOER2 binding site and contains five Sec residues that are conserved across vertebrate species. Several species of amphibians also have an additional Sec residue in the C-terminal end of this region (Lobanov, Hatfield & Gladyshev, 2008). The proposed heparin binding sites/histidine rich regions are based on rat SEPP1 found by Hondal et al. (2001). Similar histidine rich regions are found in the SEPP1’s of other species (selenodb.org). Cys residues outside the C-terminal domain are not shown. Red lines, conserved Sec residues; Black lines, Cys or Sec residues; Green lines, Cys/Sec residues within the APOER2 binding site; Green box grids, proposed heparin binding sites.

Figure 2. The relationship between the selenocysteine content of selenoprotein P and selenium requirements in vertebrates.

The solid line with the solid circles (●) is the best fit model for the SEPP1 Sec content versus Se requirements (mg Se/kg dry matter (DM)) from 14 species with representatives from the mammalian bird and bony fish classes where the genome sequences were available (second order polynomial, R² = 0.78, y = 3.3 + 93x − 175x²). The broken line represents the same data modeled with an additional five bony fish species with known Se requirement levels (  ), but unannotated genomes. SEPP1 Sec content in these fish were assumed to be within the likely range of 15–17 Sec residues found for fish in general (5PL Asymmetric sigmoidal, R² = 0.86, y = − 9.98 + (26.9/((1 + 10((−2.23397 − X) × 4.661))1.9¹⁰)). Shaded boxes group animals within classes. The X axis is log transformed.