Structural basis for the major role of O-phosphoseryl-tRNA kinase in the UGA-specific encoding of selenocysteine.
The 21(st) amino acid, selenocysteine (Sec), is assigned to the codon UGA and is biosynthesized on the selenocysteine-specific tRNA (tRNA(Sec)) with the corresponding anticodon. In archaea/eukarya, tRNA(Sec) is ligated with serine by seryl-tRNA synthetase (SerRS), the seryl moiety is phosphorylated by O-phosphoseryl-tRNA kinase (PSTK), and the phosphate group is replaced with selenol by Sep-tRNA:Sec-tRNA synthase. PSTK selectively phosphorylates seryl-tRNA(Sec), while SerRS serylates both tRNA(Ser) and tRNA(Sec). In this study, we determined the crystal structures of the archaeal tRNA(Sec).PSTK complex. PSTK consists of two independent linker-connected domains, the N-terminal catalytic domain (NTD) and the C-terminal domain (CTD). The D-arm.CTD binding occurs independently of and much more strongly than the acceptor-arm.NTD binding. PSTK thereby distinguishes the characteristic D arm with the maximal stem and the minimal loop of tRNA(Sec) from the canonical D arm of tRNA(Ser), without interacting with the anticodon. This mechanism is essential for the UGA-specific encoding of selenocysteine.
Chiba
Shiho
S
Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
Itoh
Yuzuru
Y
Sekine
Shun-ichi
S
Yokoyama
Shigeyuki
S
D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017017:Methanococcus / Q000201:enzymology* / Q000235:genetics; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D019642:RNA, Archaeal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012345:RNA, Transfer, Amino Acid-Specific / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
D019843:Archaeal Proteins; D019642:RNA, Archaeal; D012345:RNA, Transfer, Amino Acid-Specific; C036928:tRNA, selenocysteine-; D017853:Phosphotransferases (Alcohol Group Acceptor); C041177:seryl-tRNA-ATP phosphotransferase