The human SepSecS-tRNASec complex reveals the mechanism of selenocysteine formation.

Publication Type:

Journal Article

Authors:

Palioura, Sotiria; Sherrer, R Lynn; Steitz, Thomas A; Söll, Dieter; Simonovic, Miljan

Source:

Science, Volume 325, Issue 5938, p.321-5 (2009)

Keywords:

Amino Acyl-tRNA Synthetases, Base Sequence, Biocatalysis, Catalytic Domain, Crystallography, X-Ray, Humans, Hydrogen Bonding, Models, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, Phosphates, Phosphoserine, Protein Conformation, Protein Multimerization, Protein Structure, Secondary, RNA, Transfer, Amino Acid-Specific, RNA, Transfer, Amino Acyl, Selenocysteine

Abstract:

<p>Selenocysteine is the only genetically encoded amino acid in humans whose biosynthesis occurs on its cognate transfer RNA (tRNA). O-Phosphoseryl-tRNA:selenocysteinyl-tRNA synthase (SepSecS) catalyzes the final step of selenocysteine formation by a poorly understood tRNA-dependent mechanism. The crystal structure of human tRNA(Sec) in complex with SepSecS, phosphoserine, and thiophosphate, together with in vivo and in vitro enzyme assays, supports a pyridoxal phosphate-dependent mechanism of Sec-tRNA(Sec) formation. Two tRNA(Sec) molecules, with a fold distinct from other canonical tRNAs, bind to each SepSecS tetramer through their 13-base pair acceptor-TPsiC arm (where Psi indicates pseudouridine). The tRNA binding is likely to induce a conformational change in the enzyme's active site that allows a phosphoserine covalently attached to tRNA(Sec), but not free phosphoserine, to be oriented properly for the reaction to occur.</p>