7SYQ

Structure of the wt IRES and 40S ribosome ternary complex, open conformation. Structure 11(wt)

7SYQ の概要

• エントリーDOI: 10.2210/pdb7syq/pdb
• EMDBエントリー: 25537
• 分子名称: 18S rRNA, eS7, eS8, ... (38 entities in total)
• 機能のキーワード: hcv, ires, 40s, ribosome
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 37
• 化学式量合計: 1406271.67

構造登録者

Brown, Z.P.,Abaeva, I.S.,De, S.,Hellen, C.U.T.,Pestova, T.V.,Frank, J. (登録日: 2021-11-25, 公開日: 2022-07-27, 最終更新日: 2024-10-16)

主引用文献

Brown, Z.P.,Abaeva, I.S.,De, S.,Hellen, C.U.T.,Pestova, T.V.,Frank, J.
Molecular architecture of 40S translation initiation complexes on the hepatitis C virus IRES.
Embo J., 41:e110581-e110581, 2022

PubMed Abstract: Hepatitis C virus mRNA contains an internal ribosome entry site (IRES) that mediates end-independent translation initiation, requiring a subset of eukaryotic initiation factors (eIFs). Biochemical studies revealed that direct binding of the IRES to the 40S ribosomal subunit places the initiation codon into the P site, where it base pairs with eIF2-bound Met-tRNAiMet forming a 48S initiation complex. Subsequently, eIF5 and eIF5B mediate subunit joining, yielding an elongation-competent 80S ribosome. Initiation can also proceed without eIF2, in which case Met-tRNAiMet is recruited directly by eIF5B. However, the structures of initiation complexes assembled on the HCV IRES, the transitions between different states, and the accompanying conformational changes have remained unknown. To fill these gaps, we now obtained cryo-EM structures of IRES initiation complexes, at resolutions up to 3.5 Å, that cover all major stages from the initial ribosomal association, through eIF2-containing 48S initiation complexes, to eIF5B-containing complexes immediately prior to subunit joining. These structures provide insights into the dynamic network of 40S/IRES contacts, highlight the role of IRES domain II, and reveal conformational changes that occur during the transition from eIF2- to eIF5B-containing 48S complexes and prepare them for subunit joining.

PubMed: 35822879
DOI: 10.15252/embj.2022110581

実験手法

ELECTRON MICROSCOPY (3.8 Å)