ArticleInternational journal of biological macromolecules2022
Insights into the specificity for the interaction of the promiscuous SARS-CoV-2 nucleocapsid protein N-terminal domain with deoxyribonucleic acids.
Article in International journal of biological macromolecules, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 40 citations in OpenAlex.
- Peptide ligands to explore interactions with intrinsically disordered multidomain proteins: the case of SARS-CoV-2 nucleocapsid protein.Scientific reports · 2026Article
- Mechanism of SARS-CoV-2 Nucleocapsid Protein Phosphorylation-Induced Functional Switch.Viruses · 2026Article
- The regulatory mechanisms of SARS-CoV-2 N protein helicase and its annealing activity.iScience · 2025Article
- Phosphorylation Changes SARS-CoV-2 Nucleocapsid Protein's Structural Dynamics and Its Interaction With RNA.Proteins · 2025Article
- SARS-CoV-2 nucleocapsid protein directly prevents cGAS-DNA recognition through competitive binding.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Revealing the Potential of a Chimaera: a Peptide-Peptide Nucleic Acid Molecule Designed To Interact with the SARS-CoV-2 Nucleocapsid Protein.Angewandte Chemie (International ed. in English) · 2025Article
- The SARS-CoV-2 nucleocapsid protein interferes with the full enzymatic activation of UPF1 and its interaction with UPF2.Nucleic acids research · 2025Article
- Coupling of SARS-CoV-2 to Amyloid Fibrils and Liquid-Liquid Phase Separation.Current protein & peptide science · 2025Review
- Prediction of virus-host associations using protein language models and multiple instance learning.PLoS computational biology · 2024Article
- Phosphorylation in the Ser/Arg-rich region of the nucleocapsid of SARS-CoV-2 regulates phase separation by inhibiting self-association of a distant helix.The Journal of biological chemistry · 2024Article
- Brain Pathology in COVID-19: Clinical Manifestations and Potential Mechanisms.Neuroscience bulletin · 2024Review
- Liquid-liquid phase separation: a new perspective on respiratory diseases.Frontiers in immunology · 2024Review
- RNA structure and multiple weak interactions balance the interplay between RNA binding and phase separation of SARS-CoV-2 nucleocapsid.PNAS nexus · 2023Article
- The preference signature of the SARS-CoV-2 Nucleocapsid NTD for its 5'-genomic RNA elements.Nature communications · 2023Article
- A hybrid structure determination approach to investigate the druggability of the nucleocapsid protein of SARS-CoV-2.Nucleic acids research · 2023Article
- Phase-separated nucleocapsid protein of SARS-CoV-2 suppresses cGAS-DNA recognition by disrupting cGAS-G3BP1 complex.Signal transduction and targeted therapy · 2023Article
- Interaction of SARS-CoV-2 Nucleocapsid Protein and Human RNA Helicases DDX1 and DDX3X Modulates Their Activities on Double-Stranded RNA.International journal of molecular sciences · 2023Article
- Structural domains of SARS-CoV-2 nucleocapsid protein coordinate to compact long nucleic acid substrates.Nucleic acids research · 2023Article
- The Role of Disordered Regions in Orchestrating the Properties of Multidomain Proteins: The SARS-CoV-2 Nucleocapsid Protein and Its Interaction with Enoxaparin.Biomolecules · 2022Article
- Structural dynamics of SARS-CoV-2 nucleocapsid protein induced by RNA binding.PLoS computational biology · 2022Article
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Authors and funding
27 authors at 4 institutions in 1 country.
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Abstract
The SARS-CoV-2 nucleocapsid protein (N) is a multifunctional promiscuous nucleic acid-binding protein, which plays a major role in nucleocapsid assembly and discontinuous RNA transcription, facilitating the template switch of transcriptional regulatory sequences (TRS). Here, we dissect the structural features of the N protein N-terminal domain (N-NTD) and N-NTD plus the SR-rich motif (N-NTD-SR) upon binding to single and double-stranded TRS DNA, as well as their activities for dsTRS melting and TRS-induced liquid-liquid phase separation (LLPS). Our study gives insights on the specificity for N-NTD(-SR) interaction with TRS. We observed an approximation of the triple-thymidine (TTT) motif of the TRS to β-sheet II, giving rise to an orientation difference of ~25° between dsTRS and non-specific sequence (dsNS). It led to a local unfavorable energetic contribution that might trigger the melting activity. The thermodynamic parameters of binding of ssTRSs and dsTRS suggested that the duplex dissociation of the dsTRS in the binding cleft is entropically favorable. We showed a preference for TRS in the formation of liquid condensates when compared to NS. Moreover, our results on DNA binding may serve as a starting point for the design of inhibitors, including aptamers, against N, a possible therapeutic target essential for the virus infectivity.
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