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

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Abstract
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 α/β 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.