8F2E

Crystal Structure of the CoV-Y domain of SARS-CoV-2 Nonstructural Protein 3

Summary for 8F2E

• Entry DOI: 10.2210/pdb8f2e/pdb
• Descriptor: Papain-like protease nsp3, GLYCEROL (3 entities in total)
• Functional Keywords: covid-19, conronavirus, nonstructural proteins, protein structure, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, 2019-nCoV, COVID-19 virus)
• Total number of polymer chains: 1
• Total formula weight: 32160.50

Authors

Li, Y.,Shi, W.,Hao, B. (deposition date: 2022-11-07, release date: 2023-03-08, Last modification date: 2024-04-03)

Primary citation

Li, Y.,Pustovalova, Y.,Shi, W.,Gorbatyuk, O.,Sreeramulu, S.,Schwalbe, H.,Hoch, J.C.,Hao, B.
Crystal structure of the CoV-Y domain of SARS-CoV-2 nonstructural protein 3.
Sci Rep, 13:2890-2890, 2023

PubMed Abstract: Replication of the coronavirus genome starts with the formation of viral RNA-containing double-membrane vesicles (DMV) following viral entry into the host cell. The multi-domain nonstructural protein 3 (nsp3) is the largest protein encoded by the known coronavirus genome and serves as a central component of the viral replication and transcription machinery. Previous studies demonstrated that the highly-conserved C-terminal region of nsp3 is essential for subcellular membrane rearrangement, yet the underlying mechanisms remain elusive. Here we report the crystal structure of the CoV-Y domain, the most C-terminal domain of the SARS-CoV-2 nsp3, at 2.4 Å-resolution. CoV-Y adopts a previously uncharacterized V-shaped fold featuring three distinct subdomains. Sequence alignment and structure prediction suggest that this fold is likely shared by the CoV-Y domains from closely related nsp3 homologs. NMR-based fragment screening combined with molecular docking identifies surface cavities in CoV-Y for interaction with potential ligands and other nsps. These studies provide the first structural view on a complete nsp3 CoV-Y domain, and the molecular framework for understanding the architecture, assembly and function of the nsp3 C-terminal domains in coronavirus replication. Our work illuminates nsp3 as a potential target for therapeutic interventions to aid in the on-going battle against the COVID-19 pandemic and diseases caused by other coronaviruses.

PubMed: 36801935
DOI: 10.1038/s41598-023-30045-9

Experimental method

X-RAY DIFFRACTION (2.43 Å)