The structure of the TrmE GTP-binding protein and its implications for tRNA modification

EMBO J. 2005 Jan 12;24(1):23-33. doi: 10.1038/sj.emboj.7600507. Epub 2004 Dec 16.


TrmE is a 50 kDa guanine nucleotide-binding protein conserved between bacteria and man. It is involved in the modification of uridine bases (U34) at the first anticodon (wobble) position of tRNAs decoding two-family box triplets. The precise role of TrmE in the modification reaction is hitherto unknown. Here, we report the X-ray structure of TrmE from Thermotoga maritima. The structure reveals a three-domain protein comprising the N-terminal alpha/beta domain, the central helical domain and the G domain, responsible for GTP binding and hydrolysis. The N-terminal domain induces dimerization and is homologous to the tetrahydrofolate-binding domain of N,N-dimethylglycine oxidase. Biochemical and structural studies show that TrmE indeed binds formyl-tetrahydrofolate. A cysteine residue, necessary for modification of U34, is located close to the C1-group donor 5-formyl-tetrahydrofolate, suggesting a direct role of TrmE in the modification analogous to DNA modification enzymes. We propose a reaction mechanism whereby TrmE actively participates in the formylation reaction of uridine and regulates the ensuing hydrogenation reaction of a Schiff's base intermediate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Crystallography, X-Ray
  • GTP-Binding Proteins / chemistry*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Protein Structure, Secondary*
  • Protein Structure, Tertiary*
  • RNA, Transfer / metabolism*
  • Sequence Alignment
  • Tetrahydrofolates / metabolism
  • Uridine / chemistry
  • Uridine / metabolism


  • Bacterial Proteins
  • TRME protein, Thermotoga maritima
  • Tetrahydrofolates
  • Guanosine Diphosphate
  • 5,6,7,8-tetrahydrofolic acid
  • Guanosine Triphosphate
  • RNA, Transfer
  • GTP-Binding Proteins
  • Uridine

Associated data

  • PDB/1XZP
  • PDB/1XZQ