Structure of tRNA methyltransferase complex of Trm7 and Trm734 reveals a novel binding interface for tRNA recognition

The complex between Trm7 and Trm734 (Trm7–Trm734) from Saccharomyces cerevisiae catalyzes 2′-O-methylation at position 34 in tRNA. We report biochemical and structural studies of the Trm7–Trm734 complex. Purified recombinant Trm7–Trm734 preferentially methylates tRNAPhe transcript variants possessing two of three factors (Cm32, m1G37 and pyrimidine34). Therefore, tRNAPhe, tRNATrp and tRNALeu are specifically methylated by Trm7–Trm734. We have solved the crystal structures of the apo and S-adenosyl-L-methionine bound forms of Trm7–Trm734. Small angle X-ray scattering reveals that Trm7–Trm734 exists as a hetero-dimer in solution. Trm7 possesses a Rossmann-fold catalytic domain, while Trm734 consists of three WD40 β-propeller domains (termed BPA, BPB and BPC). BPA and BPC form a unique V-shaped cleft, which docks to Trm7. The C-terminal region of Trm7 is required for binding to Trm734. The D-arm of substrate tRNA is required for methylation by Trm7–Trm734. If the D-arm in tRNAPhe is docked onto the positively charged area of BPB in Trm734, the anticodon-loop is located near the catalytic pocket of Trm7. This model suggests that Trm734 is required for correct positioning of tRNA for methylation. Additionally, a point-mutation in Trm7, which is observed in FTSJ1 (human Trm7 ortholog) of nosyndromic X-linked intellectual disability patients, decreases the methylation activity.