ArticleScientific reports2017
Discovery of a junctional epitope antibody that stabilizes IL-6 and gp80 protein:protein interaction and modulates its downstream signaling.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
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- Homology Modeling in the Twilight Zone: Improved Accuracy by Sequence Space Analysis.Methods in molecular biology (Clifton, N.J.) · 2023Article
- A Hybrid Soluble gp130/Spike-Nanobody Fusion Protein Simultaneously Blocks Interleukin-6Journal of virology · 2022Article
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- The IL6-like Cytokine Family: Role and Biomarker Potential in Breast Cancer.Journal of personalized medicine · 2021Review
- Molecular mechanism of Epicedium treatment for depression based on network pharmacology and molecular docking technology.BMC complementary medicine and therapies · 2021Article
- A Molecular Communications System for the Detection of Inflammatory Levels Related to COVID-19 Disease.IEEE transactions on molecular, biological, and multi-scale communications · 2021Article
- Transcriptional profiling of intervertebral disc in a post-traumatic early degeneration organ culture model.JOR spine · 2021Article
- Research advances in hydrogen-deuterium exchange mass spectrometry for protein epitope mapping.Analytical and bioanalytical chemistry · 2021Review
- Structural Understanding of Interleukin 6 Family Cytokine Signaling and Targeted Therapies: Focus on Interleukin 11.Frontiers in immunology · 2020Review
- A strategy for the selection of monovalent antibodies that span protein dimer interfaces.The Journal of biological chemistry · 2019Article
- Recommendations for performing, interpreting and reporting hydrogen deuterium exchange mass spectrometry (HDX-MS) experiments.Nature methods · 2019Review
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein:protein interactions are fundamental in living organism homeostasis. Here we introduce VHH6, a junctional epitope antibody capable of specifically recognizing a neo-epitope when two proteins interact, albeit transiently, to form a complex. Orthogonal biophysical techniques have been used to prove the "junctional epitope" nature of VHH6, a camelid single domain antibody recognizing the IL-6-gp80 complex but not the individual components alone. X-ray crystallography, HDX-MS and SPR analysis confirmed that the CDR regions of VHH6 interact simultaneously with IL-6 and gp80, locking the two proteins together. At the cellular level, VHH6 was able to alter the response of endothelial cells to exogenous IL-6, promoting a sustained STAT3 phosphorylation signal, an accumulation of IL-6 in vesicles and an overall pro-inflammatory phenotype supported further by transcriptomic analysis. Junctional epitope antibodies, like VHH6, not only offer new opportunities in screening and structure-aided drug discovery, but could also be exploited as therapeutics to modulate complex protein:protein interactions.
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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.