SNAP output for PDB entry 8p7c [SNAP web server]

PDB-id

8p7c; SNAP-derived features in text and JSON formats; DNAproDB

Class

RNA binding protein

Method

cryo-EM (3.7 Å)

Summary

Cryoem structure of mettl6 trna serrs complex in a 2:2:2 stoichiometry

Reference

Throll P, G Dolce L, Rico-Lastres P, Arnold K, Tengo L, Basu S, Kaiser S, Schneider R, Kowalinski E (2024): "Structural basis of tRNA recognition by the m 3 C RNA methyltransferase METTL6 in complex with SerRS seryl-tRNA synthetase." Nat.Struct.Mol.Biol., 31, 1614-1624. doi: 10.1038/s41594-024-01341-3.

Abstract

Methylation of cytosine 32 in the anticodon loop of tRNAs to 3-methylcytosine (m₃C) is crucial for cellular translation fidelity. Misregulation of the RNA methyltransferases setting this modification can cause aggressive cancers and metabolic disturbances. Here, we report the cryo-electron microscopy structure of the human m₃C tRNA methyltransferase METTL6 in complex with seryl-tRNA synthetase (SerRS) and their common substrate tRNA_Ser. Through the complex structure, we identify the tRNA-binding domain of METTL6. We show that SerRS acts as the tRNA_Ser substrate selection factor for METTL6. We demonstrate that SerRS augments the methylation activity of METTL6 and that direct contacts between METTL6 and SerRS are necessary for efficient tRNA_Ser methylation. Finally, on the basis of the structure of METTL6 in complex with SerRS and tRNA_Ser, we postulate a universal tRNA-binding mode for m₃C RNA methyltransferases, including METTL2 and METTL8, suggesting that these mammalian paralogs use similar ways to engage their respective tRNA substrates and cofactors.