ArticleNature communications2022
Structural basis for Sarbecovirus ORF6 mediated blockage of nucleocytoplasmic transport.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 36 citations in OpenAlex.
- Targeting SARS-CoV-2 Structural and Accessory Proteins: Emerging Opportunities for Small-Molecule Coronavirus Antivirals.Pharmaceutics · 2026Review
- The ORF6 accessory protein contributes to SARS-CoV-2 virulence and pathogenicity in the naturally susceptible feline model of infection.Journal of virology · 2026Article
- Breaking barriers: Respiratory viral strategies targeting the host's nuclear pore complex and nuclear transport pathways.Molecular biology of the cell · 2026Review
- The evolutionary arms race on the Z-form-nucleic- acid-binding protein 1 front: endogenous Z-RNA as a self-danger signal.Molecular biomedicine · 2026Article
- A Comprehensive View on the Mechanisms of Coronavirus Escaping Innate Immunity.Veterinary sciences · 2025Review
- Viral interference of nucleocytoplasmic transport.The Journal of biological chemistry · 2025Review
- The NSP5, ORF6 and NSP13 of SARS-CoV-2 Cooperate to Modulate Inflammatory Cell Death Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- ThebioRxiv : the preprint server for biology · 2025Article
- M-Motif, a potential non-conventional NLS in YAP/TAZ and other cellular and viral proteins that inhibits classic protein import.iScience · 2025Article
- Nuclear warfare: pathogen manipulation of the nuclear pore complex and nuclear functions.mBio · 2025Review
- Hidden players of COVID-19: the evolving roles of SARS-CoV-2 accessory proteins.Frontiers in immunology · 2025Review
- Strategies Used by SARS-CoV-2 to Evade the Innate Immune System in an Evolutionary Perspective.Pathogens (Basel, Switzerland) · 2024Review
- An integrative characterization of proline cis and trans conformers in a disordered peptide.Biophysical journal · 2024Article
- SARS-CoV-2 ORF10 hijacking ubiquitination machinery reveals potential unique drug targeting sites.Acta pharmaceutica Sinica. B · 2024Article
- Upping the ante: enhanced expression of interferon-antagonizing ORF6 and ORF9b proteins by SARS-CoV-2 variants of concern.Current opinion in microbiology · 2024Review
- Article
- SARS-CoV-2 Orf6 is positioned in the nuclear pore complex by Rae1 to inhibit nucleocytoplasmic transport.Molecular biology of the cell · 2024Article
- ACE2-dependent and -independent SARS-CoV-2 entries dictate viral replication and inflammatory response during infection.Nature cell biology · 2024Article
- Article
- Interferon-International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The emergence of heavily mutated SARS-CoV-2 variants of concern (VOCs) place the international community on high alert. In addition to numerous mutations that map in the spike protein of VOCs, expression of the viral accessory proteins ORF6 and ORF9b also elevate; both are potent interferon antagonists. Here, we present the crystal structures of Rae1-Nup98 in complex with the C-terminal tails (CTT) of SARS-CoV-2 and SARS-CoV ORF6 to 2.85 Å and 2.39 Å resolution, respectively. An invariant methionine (M) 58 residue of ORF6 CTT extends its side chain into a hydrophobic cavity in the Rae1 mRNA binding groove, resembling a bolt-fitting-hole; acidic residues flanking M58 form salt-bridges with Rae1. Our mutagenesis studies identify key residues of ORF6 important for its interaction with Rae1-Nup98 in vitro and in cells, of which M58 is irreplaceable. Furthermore, we show that ORF6-mediated blockade of mRNA and STAT1 nucleocytoplasmic transport correlate with the binding affinity between ORF6 and Rae1-Nup98. Finally, binding of ORF6 to Rae1-Nup98 is linked to ORF6-induced interferon antagonism. Taken together, this study reveals the molecular basis for the antagonistic function of Sarbecovirus ORF6, and implies a strategy of using ORF6 CTT-derived peptides for immunosuppressive drug development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.