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. Author manuscript; available in PMC: 2023 Jul 4.
Published in final edited form as: Nature. 2023 Jan 4;613(7943):383–390. doi: 10.1038/s41586-022-05565-5

Fig. 4: Detailed view of the active site.

Fig. 4:

a-b, View of the tRNA variable near METTL1. RNA (yellow) and METTL1 (blue) are shown with transparent surface representation and cartoon, and SAH is shown in magenta. The variable loop is indicated with nucleotide numbers. The gap in apo state is filled as G46 is released from the helical stack and buried in the catalytic pocket after binding SAH. The orientation is the same as in (a). c. Twisting near the variable loop exposes G46 and rotates the anticodon arm relative to the rest of the tRNA. d, R24 of METTL1 occupies the space left behind by G46 to stack between A21 and A9. e, View of G46 base surrounded by a triad of acidic residues next to SAH. N7 position is indicated with an arrow, and side chains are shown only for the residues within 4 Å of RNA. f, Distance between the sulfur in SAH and N7 in G46 is indicated with an arrow. g-i, In vitro methylation activity of METTL1-WDR4 for tRNALys with point mutations in METTL1 (g) or tRNALys (h), or with wild-type proteins and different human tRNAs (i). All bar graphs are shown as mean ± SD from 3 replicates.