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

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.