6YXJ

Crystal structure of SARS-CoV macrodomain II in complex with human Paip1

Summary for 6YXJ

• Entry DOI: 10.2210/pdb6yxj/pdb
• Descriptor: Non-structural protein 3, Polyadenylate-binding protein-interacting protein 1 (2 entities in total)
• Functional Keywords: coronavirus, virus-host interaction, macrodomain fold, heat repeats., viral protein
• Biological source: Severe acute respiratory syndrome coronavirus (SARS-CoV); More
• Total number of polymer chains: 2
• Total formula weight: 42248.32

Authors

Lei, J.,Hilgenfeld, R. (deposition date: 2020-05-02, release date: 2021-03-17, Last modification date: 2024-06-19)

Primary citation

Lei, J.,Ma-Lauer, Y.,Han, Y.,Thoms, M.,Buschauer, R.,Jores, J.,Thiel, V.,Beckmann, R.,Deng, W.,Leonhardt, H.,Hilgenfeld, R.,von Brunn, A.
The SARS-unique domain (SUD) of SARS-CoV and SARS-CoV-2 interacts with human Paip1 to enhance viral RNA translation.
Embo J., 40:e102277-e102277, 2021

PubMed Abstract: The ongoing outbreak of severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) demonstrates the continuous threat of emerging coronaviruses (CoVs) to public health. SARS-CoV-2 and SARS-CoV share an otherwise non-conserved part of non-structural protein 3 (Nsp3), therefore named as "SARS-unique domain" (SUD). We previously found a yeast-2-hybrid screen interaction of the SARS-CoV SUD with human poly(A)-binding protein (PABP)-interacting protein 1 (Paip1), a stimulator of protein translation. Here, we validate SARS-CoV SUD:Paip1 interaction by size-exclusion chromatography, split-yellow fluorescent protein, and co-immunoprecipitation assays, and confirm such interaction also between the corresponding domain of SARS-CoV-2 and Paip1. The three-dimensional structure of the N-terminal domain of SARS-CoV SUD ("macrodomain II", Mac2) in complex with the middle domain of Paip1, determined by X-ray crystallography and small-angle X-ray scattering, provides insights into the structural determinants of the complex formation. In cellulo, SUD enhances synthesis of viral but not host proteins via binding to Paip1 in pBAC-SARS-CoV replicon-transfected cells. We propose a possible mechanism for stimulation of viral translation by the SUD of SARS-CoV and SARS-CoV-2.

PubMed: 33876849
DOI: 10.15252/embj.2019102277

Experimental method

X-RAY DIFFRACTION (3.5 Å)