8P7B

CryoEM structure of METTL6 tRNA SerRS complex in a 1:2:2 stoichiometry

Summary for 8P7B

• Entry DOI: 10.2210/pdb8p7b/pdb
• Related: 8OWX 8OWY
• EMDB information: 17528
• Descriptor: Serine--tRNA ligase, cytoplasmic, tRNA N(3)-methylcytidine methyltransferase METTL6, Serine tRNA, ... (7 entities in total)
• Functional Keywords: mettl6, trna, serrs, serine trna, 3-methylcytosine, rna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 206709.83

Authors

Throll, P.,Dolce, L.G.,Kowalinski, E. (deposition date: 2023-05-30, release date: 2024-06-12, Last modification date: 2024-10-30)

Primary citation

Throll, P.,G Dolce, L.,Rico-Lastres, P.,Arnold, K.,Tengo, L.,Basu, S.,Kaiser, S.,Schneider, R.,Kowalinski, E.
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, 2024

PubMed Abstract: Methylation of cytosine 32 in the anticodon loop of tRNAs to 3-methylcytosine (mC) 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 mC tRNA methyltransferase METTL6 in complex with seryl-tRNA synthetase (SerRS) and their common substrate tRNA. Through the complex structure, we identify the tRNA-binding domain of METTL6. We show that SerRS acts as the tRNA 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 methylation. Finally, on the basis of the structure of METTL6 in complex with SerRS and tRNA, we postulate a universal tRNA-binding mode for mC RNA methyltransferases, including METTL2 and METTL8, suggesting that these mammalian paralogs use similar ways to engage their respective tRNA substrates and cofactors.

PubMed: 38918637
DOI: 10.1038/s41594-024-01341-3

Experimental method

ELECTRON MICROSCOPY (2.42 Å)