N-terminal domain of TrmE, a tRNA modification GTPaseThis family contains the N-terminal domain of TrmE (also known as MnmE, ThdF, MSS1), a guanine nucleotide-binding protein conserved in all three kingdoms of life. It is involved in the modification of uridine bases (U34) at the first anticodon (wobble) position of tRNAs decoding two-family box triplets. TrmE is a three-domain protein comprising an N-terminal alpha/beta domain, a helical domain, and the GTPase domain which is nested within the helical domain. The N-terminal domain induces dimerization for self-assembly and is topologically homologous to the tetrahydrofolate (THF)-binding domain of N,N-dimethylglycine oxidase (DMGO). However, the THF-binding site in DMGO is encoded on a single polypeptide, while homodimerization would be required to create a similar THF-binding site in TrmE. Dimerization also creates a second, symmetry-related THF-binding site. Biochemical and structural studies show that TrmE indeed binds formyl-THF. 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.