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-Structure paper
| タイトル | Cryo-EM structures of the human Elongator complex at work. |
|---|---|
| ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 4094, Year 2024 |
| 掲載日 | 2024年5月15日 |
著者 | Nour-El-Hana Abbassi / Marcin Jaciuk / David Scherf / Pauline Böhnert / Alexander Rau / Alexander Hammermeister / Michał Rawski / Paulina Indyka / Grzegorz Wazny / Andrzej Chramiec-Głąbik / Dominika Dobosz / Bozena Skupien-Rabian / Urszula Jankowska / Juri Rappsilber / Raffael Schaffrath / Ting-Yu Lin / Sebastian Glatt / ![]() |
| PubMed 要旨 | tRNA modifications affect ribosomal elongation speed and co-translational folding dynamics. The Elongator complex is responsible for introducing 5-carboxymethyl at wobble uridine bases (cmU) in ...tRNA modifications affect ribosomal elongation speed and co-translational folding dynamics. The Elongator complex is responsible for introducing 5-carboxymethyl at wobble uridine bases (cmU) in eukaryotic tRNAs. However, the structure and function of human Elongator remain poorly understood. In this study, we present a series of cryo-EM structures of human ELP123 in complex with tRNA and cofactors at four different stages of the reaction. The structures at resolutions of up to 2.9 Å together with complementary functional analyses reveal the molecular mechanism of the modification reaction. Our results show that tRNA binding exposes a universally conserved uridine at position 33 (U), which triggers acetyl-CoA hydrolysis. We identify a series of conserved residues that are crucial for the radical-based acetylation of U and profile the molecular effects of patient-derived mutations. Together, we provide the high-resolution view of human Elongator and reveal its detailed mechanism of action. |
リンク | Nat Commun / PubMed:38750017 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.87 - 4.25 Å |
| 構造データ | EMDB-17924, PDB-8ptx: EMDB-17925, PDB-8pty: EMDB-17926, PDB-8ptz: EMDB-17927, PDB-8pu0: |
| 化合物 | ![]() ChemComp-SF4: ![]() ChemComp-5AD: ![]() ChemComp-ACO: ![]() ChemComp-MET: ![]() ChemComp-MG: ![]()
ChemComp-A2U: ![]() ChemComp-DCA: |
| 由来 |
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キーワード | TRANSLATION / Elongator / tRNA modification / acetyl-CoA hydrolysis |
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homo sapiens (ヒト)
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