8PU0

Cryo-EM structure of human Elp123 in complex with tRNA, desulpho-CoA, 5'-deoxyadenosine and methionine

8PU0 の概要

• エントリーDOI: 10.2210/pdb8pu0/pdb
• EMDBエントリー: 17927
• 分子名称: Elongator complex protein 1, Elongator complex protein 2, Elongator complex protein 3, ... (8 entities in total)
• 機能のキーワード: elongator, trna modification, acetyl-coa hydrolysis, translation
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 484728.07

構造登録者

Abbassi, N.,Jaciuk, M.,Lin, T.-Y.,Glatt, S. (登録日: 2023-07-16, 公開日: 2024-04-17, 最終更新日: 2024-05-22)

主引用文献

Abbassi, N.E.,Jaciuk, M.,Scherf, D.,Bohnert, P.,Rau, A.,Hammermeister, A.,Rawski, M.,Indyka, P.,Wazny, G.,Chramiec-Glabik, A.,Dobosz, D.,Skupien-Rabian, B.,Jankowska, U.,Rappsilber, J.,Schaffrath, R.,Lin, T.Y.,Glatt, S.
Cryo-EM structures of the human Elongator complex at work.
Nat Commun, 15:4094-4094, 2024

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 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.

PubMed: 38750017
DOI: 10.1038/s41467-024-48251-y

実験手法

ELECTRON MICROSCOPY (4.25 Å)