8PPK

Bat-Hp-CoV Nsp1 and eIF1 bound to the human 40S small ribosomal subunit

8PPK の概要

• エントリーDOI: 10.2210/pdb8ppk/pdb
• 関連するPDBエントリー: 8PPL
• EMDBエントリー: 17804
• 分子名称: Eukaryotic translation initiation factor 1, 40S ribosomal protein S7, 40S ribosomal protein S8, ... (40 entities in total)
• 機能のキーワード: nsp1, mers, sars, sars-cov2, ribosome, 40s ribosomal subunit, translation inhibition, coronavirus, 43s pic, 43s pre-initiation complex, mrna channel, initiation factor, eif2, eif3, eif1, eif1a, viral protein, translation
• 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: 1271012.02

構造登録者

Schubert, K.,Karousis, E.D.,Ban, I.,Lapointe, C.P.,Leibundgut, M.,Baeumlin, E.,Kummerant, E.,Scaiola, A.,Schoenhut, T.,Ziegelmueller, J.,Puglisi, J.D.,Muehlemann, O.,Ban, N. (登録日: 2023-07-07, 公開日: 2023-10-18, 最終更新日: 2024-04-24)

主引用文献

Schubert, K.,Karousis, E.D.,Ban, I.,Lapointe, C.P.,Leibundgut, M.,Baumlin, E.,Kummerant, E.,Scaiola, A.,Schonhut, T.,Ziegelmuller, J.,Puglisi, J.D.,Muhlemann, O.,Ban, N.
Universal features of Nsp1-mediated translational shutdown by coronaviruses.
Mol.Cell, 83:3546-3557.e8, 2023

PubMed Abstract: Nonstructural protein 1 (Nsp1) produced by coronaviruses inhibits host protein synthesis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp1 C-terminal domain was shown to bind the ribosomal mRNA channel to inhibit translation, but it is unclear whether this mechanism is broadly used by coronaviruses, whether the Nsp1 N-terminal domain binds the ribosome, or how Nsp1 allows viral RNAs to be translated. Here, we investigated Nsp1 from SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), and Bat-Hp-CoV coronaviruses using structural, biophysical, and biochemical experiments, revealing a conserved role for the C-terminal domain. Additionally, the N-terminal domain of Bat-Hp-CoV Nsp1 binds to the decoding center of the 40S subunit, where it would prevent mRNA and eIF1A accommodation. Structure-based experiments demonstrated the importance of decoding center interactions in all three coronaviruses and showed that the same regions of Nsp1 are necessary for the selective translation of viral RNAs. Our results provide a mechanistic framework to understand how Nsp1 controls preferential translation of viral RNAs.

PubMed: 37802027
DOI: 10.1016/j.molcel.2023.09.002

実験手法

ELECTRON MICROSCOPY (2.98 Å)