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

Science. 2009 Jul 17;325(5938):321-5. doi: 10.1126/science.1173755.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

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


  • Phosphates
  • RNA, Transfer, Amino Acid-Specific
  • RNA, Transfer, Amino Acyl
  • selenocysteinyl-tRNA
  • tRNA, selenocysteine-
  • Selenocysteine
  • Phosphoserine
  • Amino Acyl-tRNA Synthetases
  • O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase, human
  • thiophosphoric acid

Associated data

  • PDB/3HL2