8AOU

Solution NMR structure of full-length Nsp1 from SARS-CoV-2.

Summary for 8AOU

• Entry DOI: 10.2210/pdb8aou/pdb
• NMR Information: BMRB: 34748
• Descriptor: Host translation inhibitor nsp1 (1 entity in total)
• Functional Keywords: non-structural protein host translation inhibitor, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2
• Total number of polymer chains: 1
• Total formula weight: 19929.41

Authors

Wang, Y.,Kirkpatrick, J.P.,Carlomagno, T. (deposition date: 2022-08-08, release date: 2022-12-28, Last modification date: 2024-06-19)

Primary citation

Wang, Y.,Kirkpatrick, J.,Lage, S.Z.,Carlomagno, T.
Structural insights into the activity regulation of full-length non-structural protein 1 from SARS-CoV-2.
Structure, 31:128-, 2023

PubMed Abstract: Non-structural protein 1 (Nsp1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major virulence factor and thus an attractive drug target. The last 33 amino acids of Nsp1 have been shown to bind within the mRNA entry tunnel of the 40S ribosomal subunit, shutting off host gene expression. Here, we report the solution-state structure of full-length Nsp1, which features an α/β fold formed by a six-stranded, capped β-barrel-like globular domain (N-terminal domain [NTD]), flanked by short N-terminal and long C-terminal flexible tails. The NTD has been found to be critical for 40S-mediated viral mRNA recognition and promotion of viral gene expression. We find that in free Nsp1, the NTD mRNA-binding surface is occluded by interactions with the acidic C-terminal tail, suggesting a mechanism of activity regulation based on the interplay between the folded NTD and the disordered C-terminal region. These results are relevant for drug-design efforts targeting Nsp1.

PubMed: 36610391
DOI: 10.1016/j.str.2022.12.006

Experimental method

SOLUTION NMR