The Human SepSecS-tRNA Sec Complex Reveals the Mechanism of Selenocysteine Formation

Abstract

Making Selenocysteine In humans, selenocysteine is the only amino acid that lacks its own transfer RNA (tRNA) synthetase and is synthesized on its cognate tRNA. The process involves mischarging of tRNA sec with serine, phosphorylation of the serine, and then conversion of the phosphoserine into selenocysteine by the enzyme SepSecS using selenophosphate as the selenium donor. Palioura et al. (p. 321 ) now provide insight into the mechanism of selenocysteine formation, based on the crystal structure of human tRNA sec complexed with SepSecS, phosphoserine, and thiophosphate, together with in vivo and in vitro activity assays. Binding of tRNA sec to SepSecS is required to properly orient phosphoserine attached to tRNA sec for pyroxidal phosphate–based catalysis.