ArticleNature2012
Accelerated disassembly of IgE-receptor complexes by a disruptive macromolecular inhibitor.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed, 105 citations in OpenAlex.
- Antibodies targeting a shared epitope exploit IgE allostery to drive distinct functional outcomes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
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- High-affinity omalizumab variants with optimized disruptive potency prevent anaphylaxis in vivo.The Journal of allergy and clinical immunology · 2025Article
- Structural and Functional Insights Into IgE Receptor Interactions and Disruptive Inhibition.Immunological reviews · 2025Review
- Emerging diagnostic and therapeutic opportunities in food allergy.Frontiers in immunology · 2025Review
- Utilizing surface plasmon resonance as a novel method for monitoringFrontiers in biophysics · 2024Article
- Human Lung Mast Cells: Therapeutic Implications in Asthma.International journal of molecular sciences · 2022Review
- Understanding human mast cells: lesson from therapies for allergic and non-allergic diseases.Nature reviews. Immunology · 2022Review
- Review
- Directed evolution of and structural insights into antibody-mediated disruption of a stable receptor-ligand complex.Nature communications · 2021Article
- The molecular basis of allostery in a facilitated dissociation process.Structure (London, England : 1993) · 2021Article
- Review
- Bispecific T-Cell Engagers Targeting Membrane-Bound IgE.Biomedicines · 2021Article
- Structure-guided design of ultrapotent disruptive IgE inhibitors to rapidly terminate acute allergic reactions.The Journal of allergy and clinical immunology · 2021Article
- Tuning IgE: IgE-Associating Molecules and Their Effects on IgE-Dependent Mast Cell Reactions.Cells · 2021Review
- Novel Approaches in the Inhibition of IgE-Induced Mast Cell Reactivity in Food Allergy.Frontiers in immunology · 2021Review
- A Comprehensive Approach to Urticaria: From Clinical Presentation to Modern Biological Treatments Through Pathogenesis.Advances in experimental medicine and biology · 2021Article
- Past, present, and future of anti-IgE biologics.Allergy · 2020Review
- The mechanistic and functional profile of the therapeutic anti-IgE antibody ligelizumab differs from omalizumab.Nature communications · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
IgE antibodies bind the high-affinity IgE Fc receptor (FcεRI), found primarily on mast cells and basophils, and trigger inflammatory cascades of the allergic response. Inhibitors of IgE-FcεRI binding have been identified and an anti-IgE therapeutic antibody (omalizumab) is used to treat severe allergic asthma. However, preformed IgE-FcεRI complexes that prime cells before allergen exposure dissociate extremely slowly and cannot be disrupted by strictly competitive inhibitors. IgE-Fc conformational flexibility indicated that inhibition could be mediated by allosteric or other non-classical mechanisms. Here we demonstrate that an engineered protein inhibitor, DARPin E2_79 (refs 9, 10, 11), acts through a non-classical inhibition mechanism, not only blocking IgE-FcεRI interactions, but actively stimulating the dissociation of preformed ligand-receptor complexes. The structure of the E2_79-IgE-Fc(3-4) complex predicts the presence of two non-equivalent E2_79 sites in the asymmetric IgE-FcεRI complex, with site 1 distant from the receptor and site 2 exhibiting partial steric overlap. Although the structure is indicative of an allosteric inhibition mechanism, mutational studies and quantitative kinetic modelling indicate that E2_79 acts through a facilitated dissociation mechanism at site 2 alone. These results demonstrate that high-affinity IgE-FcεRI complexes can be actively dissociated to block the allergic response and suggest that protein-protein complexes may be more generally amenable to active disruption by macromolecular inhibitors.
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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.