Structural characterization of mammalian selenoproteins

Abstract

Structural analysis of proteins is a highly informative approach to assess protein function and regulation. It can help establish catalytic mechanisms of enzymes and visualize the structural basis for their interactions with substrates and partner proteins. To date, the following mammalian selenoproteins have been structurally characterized either by X-ray crystallography or nuclear magnetic resonance spectroscopy: the 15 kDa selenoprotein, glutathione peroxidases 1, 2, 3 and 4, selenophosphate synthetase 2, selenoproteins M and W, methionine sulfoxide reductase B1, and thioredoxin reductases 1 and 3. For structural analysis of most of these proteins, the catalytic selenocysteine was mutated to cysteine or glycine, allowing high protein expression. These structures and dynamic properties of selenoproteins verified the dominance of thioredoxin fold in mammalian selenoproteins and yielded critical insights into their functions and catalytic mechanisms.