8A3D

Human mature large subunit of the ribosome with eIF6 and homoharringtonine bound

これはPDB形式変換不可エントリーです。

8A3D の概要

• エントリーDOI: 10.2210/pdb8a3d/pdb
• EMDBエントリー: 15113
• 分子名称: 28S ribosomal RNA, 60S ribosomal protein L7a, 60S ribosomal protein L9, ... (53 entities in total)
• 機能のキーワード: ribosome, human, translation, rna modifications, water, magnesium, potassium, homoharringtonine
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 45
• 化学式量合計: 2599218.10

構造登録者

Faille, A.,Warren, A.J.,Dent, K.C. (登録日: 2022-06-08, 公開日: 2023-03-08, 最終更新日: 2024-07-24)

主引用文献

Faille, A.,Dent, K.C.,Pellegrino, S.,Jaako, P.,Warren, A.J.
The chemical landscape of the human ribosome at 1.67 angstrom resolution.
Biorxiv, 2023

PubMed Abstract: The ability of ribosomes to translate the genetic code into protein requires a finely tuned ion and solvent ecosystem. However, the lack of high-resolution structures has precluded accurate positioning of all the functional elements of the ribosome and limited our understanding of the specific role of ribosomal RNA chemical modifications in modulating ribosome function in health and disease. Here, using a new sample preparation methodology based on functionalised pristine graphene-coated grids, we solve the cryo-EM structure of the human large ribosomal subunit to a resolution of 1.67 Å. The accurate assignment of water molecules, magnesium and potassium ions in our model highlights the fundamental biological role of ribosomal RNA methylation in harnessing unconventional carbon-oxygen hydrogen bonds to establish chemical interactions with the environment and fine-tune the functional interplay with tRNA. In addition, the structures of three translational inhibitors bound to the human large ribosomal subunit at better than 2 Å resolution provide mechanistic insights into how three key druggable pockets of the ribosome are targeted and illustrate the potential of this methodology to accelerate high-throughput structure-based design of anti-cancer therapeutics.

PubMed: 36909531
DOI: 10.1101/2023.02.28.530191

実験手法

ELECTRON MICROSCOPY (1.67 Å)