8OWY

Crystal structure of METTL6 mutant 40-269 bound to SAH

8OWY の概要

• エントリーDOI: 10.2210/pdb8owy/pdb
• 分子名称: tRNA N(3)-methylcytidine methyltransferase METTL6, S-ADENOSYL-L-HOMOCYSTEINE (2 entities in total)
• 機能のキーワード: trna modification, m3c, methyltransferase, rna binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 56083.94

構造登録者

Throll, P.,Basu, S.,Dolce, L.G.,Kowalinski, E. (登録日: 2023-04-28, 公開日: 2024-05-08, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3.2 Å)