ArticleNature communications2022
MERS-CoV ORF4b employs an unusual binding mechanism to target IMPα and block innate immunity.
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 22 papers.
What it found
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Who cites it
22 citing papers in PubMed, 24 citations in OpenAlex.
- Structures of Nicotiana benthamiana importin-α1 complexes reveal mechanisms for plant virus NLS recognition.The Plant journal : for cell and molecular biology · 2026Article
- Multiple roads between the nucleus and the cytoplasm: classes of linear NLSs and NESs and their receptors.Current opinion in structural biology · 2026Review
- Structural insights into the nuclear import of ovine gammaherpesvirus 2 ORF73 LANA homologue.The Journal of general virology · 2026Article
- Structural and functional characterisation of ATF2 nuclear import reveals paralogue-selective importin-α recognition and a non-canonical NLS formed in trans.Life science alliance · 2026Article
- Structural Insights Into the Nuclear Import of Gallid Alphaherpesvirus 1 Large Tegument Protein.MicrobiologyOpen · 2026Article
- MERS-CoV accessory ORF proteins in innate immune evasion: an evidence-graded functional framework.Frontiers in immunology · 2026Review
- Structural Insights Into the Nuclear Import of Marek's Disease Virus Large Tegument Protein.Advances in virology · 2026Article
- Elucidation of the binding interaction interface between AAV serotype 11 capsid protein and host nuclear import proteins.Molecular therapy. Methods & clinical development · 2025Article
- Viral interference of nucleocytoplasmic transport.The Journal of biological chemistry · 2025Review
- Structural Insights into the Nuclear Import of Haliotid Herpesvirus 1 Large Tegument Protein Homologue.Viruses · 2025Article
- Human coronaviruses: activation and antagonism of innate immune responses.Microbiology and molecular biology reviews : MMBR · 2025Review
- Anti-interferon armamentarium of human coronaviruses.Cellular and molecular life sciences : CMLS · 2025Review
- Structural basis for nuclear import of adeno-associated virus serotype 6 capsid protein.Journal of virology · 2025Article
- RNA Binding Properties of SOX Family Members.Cells · 2024Article
- Structural basis for nuclear import of bat adeno-associated virus capsid protein.The Journal of general virology · 2024Article
- Recurrent viral capture of cellular phosphodiesterases that antagonize OAS-RNase L.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Nuclear localization signal-tagged systems: relevant nuclear import principles in the context of current therapeutic design.Chemical Society reviews · 2024Review
- Review
- Recurrent Viral Capture of Cellular Phosphodiesterases that Antagonize OAS-RNase L.bioRxiv : the preprint server for biology · 2023Article
- Henipavirus Matrix Protein Employs a Non-Classical Nuclear Localization Signal Binding Mechanism.Viruses · 2023Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
Abstract
The MERS coronavirus (MERS-CoV) is a highly pathogenic, emerging virus that produces accessory proteins to antagonize the host innate immune response. The MERS-CoV ORF4b protein has been shown to bind preferentially to the nuclear import adapter IMPα3 in infected cells, thereby inhibiting NF-κB-dependent innate immune responses. Here, we report high-resolution structures of ORF4b bound to two distinct IMPα family members. Each exhibit highly similar binding mechanisms that, in both cases, lack a prototypical Lys bound at their P2 site. Mutations within the NLS region dramatically alter the mechanism of binding, which reverts to the canonical P2 Lys binding mechanism. Mutational studies confirm that the novel binding mechanism is important for its nuclear import, IMPα interaction, and inhibition of innate immune signaling pathways. In parallel, we determined structures of the nuclear binding domain of NF-κB component p50 bound to both IMPα2 and α3, demonstrating that p50 overlaps with the ORF4b binding sites, suggesting a basis for inhibition. Our results provide a detailed structural basis that explains how a virus can target the IMPα nuclear import adapter to impair immunity, and illustrate how small mutations in ORF4b, like those found in closely related coronaviruses such as HKU5, change the IMPα binding mechanism.
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Registered trials
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.