Cryo-EM structures of the human Elongator complex at work

Abbassi, Nour-el-Hana; Jaciuk, Marcin; Scherf, David; Böhnert, Pauline; Rau, Alexander; Hammermeister, Alexander; Rawski, Michał; Indyka, Paulina; Wazny, Grzegorz; Chramiec-Głąbik, Andrzej; Dobosz, Dominika; Skupien-Rabian, Bozena; Jankowska, Urszula; Rappsilber, Juri; Schaffrath, Raffael; Lin, Ting-Yu; Glatt, Sebastian

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 (cm5U34) 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 (U33), which triggers acetyl-CoA hydrolysis. We identify a series of conserved residues that are crucial for the radical-based acetylation of U34 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.

Citation

Abbassi, N., Jaciuk, M., Scherf, D., Böhnert, P., Rau, A., Hammermeister, A., …Glatt, S. (2024). Cryo-EM structures of the human Elongator complex at work. Nature Communications, 15(1), Article 4094. https://doi.org/10.1038/s41467-024-48251-y

• Journal Article Type: Article
• Acceptance Date: Apr 22, 2024
• Online Publication Date: May 15, 2024
• Publication Date: May 15, 2024
• Deposit Date: May 15, 2024
• Publicly Available Date: May 16, 2024
• Journal: Nature Communications
• Publisher: Nature Research
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 1
• Article Number: 4094
• DOI: https://doi.org/10.1038/s41467-024-48251-y
• Public URL: https://durham-repository.worktribe.com/output/2441039