ArticleJournal of molecular biology2023
Human 14-3-3 Proteins Site-selectively Bind the Mutational Hotspot Region of SARS-CoV-2 Nucleoprotein Modulating its Phosphoregulation.
Article in Journal of molecular biology, 2023. 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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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Targeting SARS-CoV-2 Structural and Accessory Proteins: Emerging Opportunities for Small-Molecule Coronavirus Antivirals.Pharmaceutics · 2026Review
- Intramolecular loops control SARS-CoV-2 nucleocapsid protein self-association and nucleic acid binding dependent on phosphorylation.bioRxiv : the preprint server for biology · 2026Article
- Article
- Phosphatase PP2A promotes RTA dephosphorylation to impair KSHV lytic replication.PLoS pathogens · 2025Article
- Evolution of a fuzzy ribonucleoprotein complex in viral assembly.bioRxiv : the preprint server for biology · 2025Article
- Phosphorylation toggles the SARS-CoV-2 nucleocapsid protein between two membrane-associated condensate states.Nature communications · 2025Article
- Dynamic interactions of dimeric hub proteins underlie their diverse functions and structures: A comparative analysis of 14-3-3 and LC8.The Journal of biological chemistry · 2025Review
- Identification ofMolecules (Basel, Switzerland) · 2025Article
- 4D-DIA Proteomics Uncovers New Insights into Host Salivary Response Following SARS-CoV-2 Omicron Infection.Journal of proteome research · 2025Article
- Genetic Code Expansion: Recent Developments and Emerging Applications.Chemical reviews · 2025Review
- The role of intrinsically disordered regions of SARS-CoV-2 nucleocapsid and non-structural protein 1 proteins.Frontiers in chemistry · 2025Review
- Look for the Scaffold: Multifaceted Regulation of Enzyme Activity by 14-3-3 Proteins.Physiological research · 2024Review
- The Disorderly Nature of Caliciviruses.Viruses · 2024Review
- Genetic Encoding of Phosphorylated Amino Acids into Proteins.Chemical reviews · 2024Review
- 14-3-3 binding motif phosphorylation disrupts Hdac4-organized condensates to stimulate cardiac reprogramming.Cell reports · 2024Article
- A viral assembly inhibitor blocks SARS-CoV-2 replication in airway epithelial cells.Communications biology · 2024Article
- Article
- Diversity of Short Linear Interaction Motifs in SARS-CoV-2 Nucleocapsid Protein.bioRxiv : the preprint server for biology · 2023Article
- A Novel Viral Assembly Inhibitor Blocks SARS-CoV-2 Replication in Airway Epithelial Cells.Research square · 2023Article
- Autonomous Synthesis of Functional, Permanently Phosphorylated Proteins for Defining the Interactome of Monomeric 14-3-3ζ.ACS central science · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Phosphorylation of SARS-CoV-2 nucleoprotein recruits human cytosolic 14-3-3 proteins playing a well-recognized role in replication of many viruses. Here we use genetic code expansion to demonstrate that 14-3-3 binding is triggered by phosphorylation of SARS-CoV-2 nucleoprotein at either of two pseudo-repeats centered at Ser197 and Thr205. According to fluorescence anisotropy measurements, the pT205-motif,presentin SARS-CoV-2 but not in SARS-CoV, is preferred over the pS197-motif by all seven human 14-3-3 isoforms, which collectively display an unforeseen pT205/pS197 peptide binding selectivity hierarchy. Crystal structures demonstrate that pS197 and pT205 are mutually exclusive 14-3-3-binding sites, whereas SAXS and biochemical data obtained on the full protein-protein complex indicate that 14-3-3 binding occludes the Ser/Arg-rich region of the nucleoprotein, inhibiting its dephosphorylation. This Ser/Arg-rich region is highly prone to mutations, as exemplified by the Omicron and Delta variants, with our data suggesting that the strength of 14-3-3/nucleoprotein interaction can be linked with the replicative fitness of the virus.
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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.