ArticlemBio2011
An insertion mutation that distorts antibody binding site architecture enhances function of a human antibody.
Article in mBio, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The trial behind it
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
33 citing papers in PubMed.
- Trial
- Antibody Hotspot-CentricACS medicinal chemistry letters · 2026Article
- Explore antibody repertoire in the era of AI.Acta biochimica et biophysica Sinica · 2025Article
- De novo design of D-peptide ligands: Application to influenza virus hemagglutinin.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular mechanisms of DNA lesion and repair during antibody somatic hypermutation.Science China. Life sciences · 2024Review
- Somatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants.Nature communications · 2023Article
- Learning the statistics and landscape of somatic mutation-induced insertions and deletions in antibodies.PLoS computational biology · 2022Article
- Contribution of rare mutational outcomes to broadly neutralizing antibodies.Acta biochimica et biophysica Sinica · 2022Review
- Article
- Affinity maturation: highlights in the application of in vitro strategies for the directed evolution of antibodies.Emerging topics in life sciences · 2021Article
- Shotgun scanning glycomutagenesis: A simple and efficient strategy for constructing and characterizing neoglycoproteins.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Modeling Immunity with Rosetta: Methods for Antibody and Antigen Design.Biochemistry · 2021Review
- In vitro evolution of antibody affinity via insertional scanning mutagenesis of an entire antibody variable region.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
- Breaking the law: unconventional strategies for antibody diversification.Nature reviews. Immunology · 2019Review
- Improvement of antibody functionality by structure-guided paratope engraftment.Nature communications · 2019Article
- Influenza Virus-Specific Human Antibody Repertoire Studies.Journal of immunology (Baltimore, Md. : 1950) · 2019Review
- Diversity of antigenic mutants of influenza A(H1N1)pdm09 virus escaped from human monoclonal antibodies.Scientific reports · 2017Article
- Influenza virus antigenicity and broadly neutralizing epitopes.Current opinion in virology · 2015Review
- Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
The structural and functional significance of somatic insertions and deletions in antibody chains is unclear. Here, we demonstrate that a naturally occurring three-amino-acid insertion within the influenza virus-specific human monoclonal antibody 2D1 heavy-chain variable region reconfigures the antibody-combining site and contributes to its high potency against the 1918 and 2009 pandemic H1N1 influenza viruses. The insertion arose through a series of events, including a somatic point mutation in a predicted hot-spot motif, introduction of a new hot-spot motif, a molecular duplication due to polymerase slippage, a deletion due to misalignment, and additional somatic point mutations. Atomic resolution structures of the wild-type antibody and a variant in which the insertion was removed revealed that the three-amino-acid insertion near the base of heavy-chain complementarity-determining region (CDR) H2 resulted in a bulge in that loop. This enlarged CDR H2 loop impinges on adjacent regions, causing distortion of the CDR H1 architecture and its displacement away from the antigen-combining site. Removal of the insertion restores the canonical structure of CDR H1 and CDR H2, but binding, neutralization activity, and in vivo activity were reduced markedly because of steric conflict of CDR H1 with the hemagglutinin antigen.
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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.