Quantifying Turnover Dynamics of Selenoproteome by Isotopic Perturbation

Selenium, as an essential trace element of life, is closely related to human health and is required to produce selenoproteins, a family of important functional proteins in many living organisms. All selenoproteins contain a special amino acid, selenocysteine, which often serves as their active-site residue, and the expression and activity of selenoproteins are fine-tuned. However, the turnover dynamics of selenoproteome has never been systematically investigated, especially in a site-specific manner for selenocysteines. In the current work, we developed a chemical proteomic strategy named SElenoprotein Turnover Rate by Isotope Perturbation (SETRIP) to quantitatively monitor the turnover dynamics of selenoproteins at the proteomic level. The kinetic rates and half-lives of nine selenoproteins were accurately measured by combining (Na2SeO3)-Se-74 metabolic labeling with pulse-chase chemoproteomics. The half-lives of selenoproteins were measured to range from 6 to 32 h with the housekeeping selenoprotein glutathione peroxidases (GPX4) showing a faster turnover rate, implying that the hierarchy regulation also exists in the turnover of selenoproteins in addition to expression and activity. Our study generated a global portrait of dynamic changes in the selenoproteome and provided important clues to study the roles of selenium in biology.

Automated summary

In this paper, a chemical proteomic strategy called SETRIP was developed to quantitatively monitor the turnover dynamics of selenoproteins at the proteomic level. The half-lives of nine selenoproteins were accurately measured, ranging from 6 to 32 hours. The study provides a global portrait of dynamic changes in the selenoproteome and suggests the existence of hierarchy regulation in the turnover of selenoproteins.