8XAB

Crystal structure of Ubl1 domain of nonstructural protein 3 of SARS-CoV-2

8XAB の概要

• エントリーDOI: 10.2210/pdb8xab/pdb
• 分子名称: Papain-like protease nsp3, GLYCEROL (3 entities in total)
• 機能のキーワード: ubl1, nonstructural protein 3, sars-cov-2, virus
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11149.57

構造登録者

Li, Y.,Ke, Z. (登録日: 2023-12-03, 公開日: 2023-12-20, 最終更新日: 2024-11-06)

主引用文献

Ke, Z.,Zhang, H.,Wang, Y.,Wang, J.,Peng, F.,Wang, J.,Liu, X.,Hu, H.,Li, Y.
N terminus of SARS-CoV-2 nonstructural protein 3 interrupts RNA-driven phase separation of N protein by displacing RNA.
J.Biol.Chem., 300:107828-107828, 2024

PubMed Abstract: The connection between SARS-CoV-2 replication-transcription complexes and nucleocapsid (N) protein is critical for regulating genomic RNA replication and virion packaging over the viral life cycle. However, the mechanism that dynamically regulates genomic RNA packaging and replication remains elusive. Here, we demonstrate that the N-terminal domain of SARS-CoV-2 nonstructural protein 3, a core component of viral replication-transcription complexes, binds N protein and displaces RNA in a concentration-dependent manner. This interaction disrupts liquid-liquid phase separation of N protein driven by N protein-RNA interactions which is crucial for virion packaging and viral replication. We also report a high-resolution crystal structure of the nonstructural protein 3 ubiquitin-like domain 1 (Ubl1) at 1.49 Å, which reveals abundant negative charges on the protein surface. Sequence and structural analyses identify several conserved motifs at the Ubl1-N protein interface and a previously unexplored highly negative groove, providing insights into the molecular mechanism of Ubl1-mediated modulation of N protein-RNA binding. Our findings elucidate the mechanism of dynamic regulation of SARS-CoV-2 genomic RNA replication and packaging over the viral life cycle. Targeting the conserved Ubl1-N protein interaction hotspots also promises to aid in the development of broad-spectrum antivirals against pathogenic coronaviruses.

PubMed: 39341499
DOI: 10.1016/j.jbc.2024.107828

実験手法

X-RAY DIFFRACTION (1.49 Å)