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-Structure paper
タイトル | Structural basis of tRNA recognition by the mC RNA methyltransferase METTL6 in complex with SerRS seryl-tRNA synthetase. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 31, Issue 10, Page 1614-1624, Year 2024 |
掲載日 | 2024年6月25日 |
著者 | Philipp Throll / Luciano G Dolce / Palma Rico-Lastres / Katharina Arnold / Laura Tengo / Shibom Basu / Stefanie Kaiser / Robert Schneider / Eva Kowalinski / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Struct Mol Biol / PubMed:38918637 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.42 - 5.6 Å |
構造データ | EMDB-17528, PDB-8p7b: EMDB-17529, PDB-8p7c: EMDB-17530, PDB-8p7d: EMDB-17531: SerRS bound to serine tRNA EMDB-17532: Serine tRNA from Trichoplusia ni PDB-8owx: PDB-8owy: |
化合物 | ChemComp-SAH: ChemComp-B3P: ChemComp-MG: ChemComp-HOH: |
由来 |
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キーワード | RNA BINDING PROTEIN / tRNA modification / m3C / methyltransferase / METTL6 / tRNA / SerRS / Serine tRNA / 3-Methylcytosine |