ArticleVirology2019
Structural characterization and biological function of bivalent binding of CD2AP to intrinsically disordered domain of chikungunya virus nsP3 protein.
Article in Virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Alphavirus nsP3 as a multifunctional orchestrator of virus-host interplay.Journal of virology · 2026Review
- Identification of mosquito proteins that differentially interact with alphavirus nonstructural protein 3, a determinant of vector specificity.PLoS neglected tropical diseases · 2023Article
- G3BP/Rin-Binding Motifs Inserted into Flexible Regions of nsP2 Support RNA Replication of Chikungunya Virus.Journal of virology · 2022Article
- Article
- Identification of a non-canonical G3BP-binding sequence in a Mayaro virus nsP3 hypervariable domain.Frontiers in cellular and infection microbiology · 2022Article
- NAP1L1 and NAP1L4 Binding to Hypervariable Domain of Chikungunya Virus nsP3 Protein Is Bivalent and Requires Phosphorylation.Journal of virology · 2021Article
- Review
- Phosphorylation Sites in the Hypervariable Domain in Chikungunya Virus nsP3 Are Crucial for Viral Replication.Journal of virology · 2021Article
- Overview on Chikungunya Virus Infection: From Epidemiology to State-of-the-Art Experimental Models.Frontiers in microbiology · 2021Review
- Novel NMR Assignment Strategy Reveals Structural Heterogeneity in Solution of the nsP3 HVD Domain of Venezuelan Equine Encephalitis Virus.Molecules (Basel, Switzerland) · 2020Article
- Structural and Functional Characterization of Host FHL1 Protein Interaction with Hypervariable Domain of Chikungunya Virus nsP3 Protein.Journal of virology · 2020Article
- Assigned NMR backbone resonances of the ligand-binding region domain of the pneumococcal serine-rich repeat protein (PsrP-BR) reveal a rigid monomer in solution.Biomolecular NMR assignments · 2020Article
- Article
- Hypervariable Domain of nsP3 of Eastern Equine Encephalitis Virus Is a Critical Determinant of Viral Virulence.Journal of virology · 2020Article
- Mutations in Hypervariable Domain of Venezuelan Equine Encephalitis Virus nsP3 Protein Differentially Affect Viral Replication.Journal of virology · 2020Article
- miR-188-5p Promotes Tumor Growth by Targeting CD2AP Through PI3K/AKT/mTOR Signaling in Children with Acute Promyelocytic Leukemia.OncoTargets and therapy · 2020Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Alphavirus nsP3 proteins contain long, intrinsically disordered, hypervariable domains, HVD, which serve as hubs for interaction with many cellular proteins. Here, we have deciphered the mechanism and function of HVD interaction with host factors in alphavirus replication. Using NMR spectroscopy, we show that CHIKV HVD contains two SH3 domain-binding sites. Using an innovative chemical shift perturbation signature approach, we demonstrate that CD2AP interaction with HVD is mediated by its SH3-A and SH3-C domains, and this leaves the SH3-B domain available for interaction with other cellular factor(s). This cooperative interaction with two SH3 domains increases binding affinity to CD2AP and possibly induces long-range allosteric effects in HVD. Our data demonstrate that BIN1, CD2AP and SH3KBP1 play redundant roles in initiation of CHIKV replication. Point mutations in both CHIKV HVD binding sites abolish its interaction with all three proteins, CD2AP, BIN1 and SH3KBP1. This results in strong inhibition of viral replication initiation.
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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.