ArticleNature communications2020
Bivalent antibody pliers inhibit β-tryptase by an allosteric mechanism dependent on the IgG hinge.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 41 citations in OpenAlex.
- Mast cell proteases and their significance in physiology, pathology, and therapeutic approaches.Pharmacological reviews · 2026Review
- Engineering Saccharomyces cerevisiae secretory system for recombinant protein production: strategies from signal peptides to protease control.Archives of microbiology · 2026Review
- Complete inhibition of β-tryptase by tetramer dissociation and active site allostery due to a single antibody residue.Nature communications · 2026Article
- Rational design of potent small-molecule SMARCA2/A4 degraders acting via the recruitment of FBXO22.Nature communications · 2025Article
- Disulfide-constrained Fabs overcome target size limitation for high-resolution single particle cryoEM.Nature communications · 2025Article
- Review
- Unveiling the functions of five recently characterized lncRNAs in cancer progression.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Integrating single cell and bulk RNA sequencing data identifies RBM17 as a novel response biomarker for immunotherapy in bladder cancer.Virchows Archiv : an international journal of pathology · 2024Article
- HPK1 citron homology domain regulates phosphorylation of SLP76 and modulates kinase domain interaction dynamics.Nature communications · 2024Article
- Development of Adenovirus-Based Covid-19 Vaccine Candidate in Indonesia.Molecular biotechnology · 2024Article
- Tryptase β regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis.Nature communications · 2023Article
- SARS-CoV-2 Antibody Effectiveness Is Influenced by Non-Epitope Mutation/Binding-Induced Denaturation of the Epitope 3D Architecture.Pathogens (Basel, Switzerland) · 2022Article
- Human Lung Mast Cells: Therapeutic Implications in Asthma.International journal of molecular sciences · 2022Review
- Investigation of SARS-CoV-2 nucleocapsid protein interaction with a specific antibody by combined spectroscopic ellipsometry and quartz crystal microbalance with dissipation.Journal of colloid and interface science · 2022Article
- Structure of the core human NADPH oxidase NOX2.Nature communications · 2022Article
- Allosteric inhibition of HTRA1 activity by a conformational lock mechanism to treat age-related macular degeneration.Nature communications · 2022Article
- Understanding human mast cells: lesson from therapies for allergic and non-allergic diseases.Nature reviews. Immunology · 2022Review
- Prognostic factors in adult brainstem glioma: a tertiary care center analysis and review of the literature.Journal of neurology · 2022Review
- Engineering, Characterization, and Biological Evaluation of an Antibody Targeting the HGF Receptor.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
Human β-tryptase, a tetrameric trypsin-like serine protease, is an important mediator of allergic inflammatory responses in asthma. Antibodies generally inhibit proteases by blocking substrate access by binding to active sites or exosites or by allosteric modulation. The bivalency of IgG antibodies can increase potency via avidity, but has never been described as essential for activity. Here we report an inhibitory anti-tryptase IgG antibody with a bivalency-driven mechanism of action. Using biochemical and structural data, we determine that four Fabs simultaneously occupy four exosites on the β-tryptase tetramer, inducing allosteric changes at the small interface. In the presence of heparin, the monovalent Fab shows essentially no inhibition, whereas the bivalent IgG fully inhibits β-tryptase activity in a hinge-dependent manner. Our results suggest a model where the bivalent IgG acts akin to molecular pliers, pulling the tetramer apart into inactive β-tryptase monomers, and may provide an alternative strategy for antibody engineering.
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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.