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Title | Cryo-EM structures of the human Elongator complex at work. |
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Journal, issue, pages | Nat Commun, Vol. 15, Issue 1, Page 4094, Year 2024 |
Publish date | May 15, 2024 |
Authors | 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 Abstract | 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. |
External links | Nat Commun / PubMed:38750017 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.87 - 4.25 Å |
Structure data | EMDB-17924, PDB-8ptx: EMDB-17925, PDB-8pty: EMDB-17926, PDB-8ptz: EMDB-17927, PDB-8pu0: |
Chemicals | ChemComp-SF4: ChemComp-5AD: ChemComp-ACO: ChemComp-MET: ChemComp-MG:
ChemComp-A2U: ChemComp-DCA: |
Source |
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Keywords | TRANSLATION / Elongator / tRNA modification / acetyl-CoA hydrolysis |