ArticleProceedings of the National Academy of Sciences of the United States of America2016
Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Article
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- Can antibody conjugated nanomicelles alter the prospect of antibody targeted therapy against schistosomiasis mansoni?PLoS neglected tropical diseases · 2023Article
- Predicting prime editing efficiency and product purity by deep learning.Nature biotechnology · 2023Article
- A human monoclonal antibody bivalently binding two different epitopes in streptococcal M protein mediates immune function.EMBO molecular medicine · 2023Article
- Phosphorylation-dependent association of human chromatin protein PC4 to linker histone H1 regulates genome organization and transcription.Nucleic acids research · 2022Article
- Engineering Binders with Exceptional Selectivity.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Contribution of Dysregulated B-Cells and IgE Antibody Responses to Multiple Sclerosis.Frontiers in immunology · 2022Review
- A comprehensive antigen production and characterisation study for easy-to-implement, specific and quantitative SARS-CoV-2 serotests.EBioMedicine · 2021Article
- Multiplex bead binding assays using off-the-shelf components and common flow cytometers.Journal of immunological methods · 2021Article
- The ACE2-binding Interface of SARS-CoV-2 Spike Inherently Deflects Immune Recognition.Journal of molecular biology · 2021Article
- SHP2 inhibition diminishes KRASG12C cycling and promotes tumor microenvironment remodeling.The Journal of experimental medicine · 2021Article
- Higher-Order Chromatin Structures of Chromosomally Integrated HHV-6A Predict Integration Sites.Frontiers in cellular and infection microbiology · 2021Article
- Targeting Phosphotyrosine in Native Proteins with Conditional, Bispecific Antibody Traps.Journal of the American Chemical Society · 2020Article
- Biology and Physics of Heterochromatin-Cells · 2020Review
- Review:Frontiers in genetics · 2020Review
- Paratope Duality and Gullying are Among the Atypical Recognition Mechanisms Used by a Trio of Nanobodies to Differentiate Ebolavirus Nucleoproteins.Journal of molecular biology · 2019Article
- Advances in the Production and Batch Reformatting of Phage Antibody Libraries.Molecular biotechnology · 2019Review
- IgM Antibodies Can Access Cryptic Antigens Denied to IgG: Hypothesis on Novel Binding Mechanism.Frontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Antibodies have a well-established modular architecture wherein the antigen-binding site residing in the antigen-binding fragment (Fab or Fv) is an autonomous and complete unit for antigen recognition. Here, we describe antibodies departing from this paradigm. We developed recombinant antibodies to trimethylated lysine residues on histone H3, important epigenetic marks and challenging targets for molecular recognition. Quantitative characterization demonstrated their exquisite specificity and high affinity, and they performed well in common epigenetics applications. Surprisingly, crystal structures and biophysical analyses revealed that two antigen-binding sites of these antibodies form a head-to-head dimer and cooperatively recognize the antigen in the dimer interface. This "antigen clasping" produced an expansive interface where trimethylated Lys bound to an unusually extensive aromatic cage in one Fab and the histone N terminus to a pocket in the other, thereby rationalizing the high specificity. A long-neck antibody format with a long linker between the antigen-binding module and the Fc region facilitated antigen clasping and achieved both high specificity and high potency. Antigen clasping substantially expands the paradigm of antibody-antigen recognition and suggests a strategy for developing extremely specific antibodies.
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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.