ArticleProceedings of the National Academy of Sciences of the United States of America2006
Antibody evolution constrains conformational heterogeneity by tailoring protein dynamics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed.
- Fitness Landscape for Antibodies 2: Benchmarking Reveals That Protein AI Models Cannot Yet Consistently Predict Developability Properties.bioRxiv : the preprint server for biology · 2025Article
- Accuracy and Reproducibility of Lipari-Szabo Order Parameters From Molecular Dynamics.The journal of physical chemistry. B · 2024Article
- Evolutionary trajectory of receptor binding specificity and promiscuity of the spike protein of SARS-CoV-2.Protein science : a publication of the Protein Society · 2022Article
- Allostery in the dynamic coactivator domain KIX occurs through minor conformational micro-states.PLoS computational biology · 2022Article
- Conformational plasticity of the HIV-1 gp41 immunodominant region is recognized by multiple non-neutralizing antibodies.Communications biology · 2022Article
- Selective Recognition of Carbohydrate Antigens by Germline Antibodies Isolated from AID Knockout Mice.Journal of the American Chemical Society · 2022Article
- Higher Affinity Antibodies Bind With Lower Hydration and Flexibility in Large Scale Simulations.Frontiers in immunology · 2022Article
- Redesigning an antibody H3 loop by virtual screening of a small library of human germline-derived sequences.Scientific reports · 2021Article
- Comparison of Huggins Coefficients and Osmotic Second Virial Coefficients of Buffered Solutions of Monoclonal Antibodies.Polymers · 2021Article
- Local and Global Rigidification Upon Antibody Affinity Maturation.Frontiers in molecular biosciences · 2020Article
- Involvement of Local, Rapid Conformational Dynamics in Binding of Flexible Recognition Motifs.The journal of physical chemistry. B · 2019Article
- Optimizing antibody affinity and stability by the automated design of the variable light-heavy chain interfaces.PLoS computational biology · 2019Article
- Structure and Dynamics of Stacking Interactions in an Antibody Binding Site.Biochemistry · 2019Article
- Breaking the law: unconventional strategies for antibody diversification.Nature reviews. Immunology · 2019Review
- Deciphering evolution of immune recognition in antibodies.BMC structural biology · 2018Article
- Allosteric Effects between the Antibody Constant and Variable Regions: A Study of IgA Fc Mutations on Antigen Binding.Antibodies (Basel, Switzerland) · 2018Article
- Conformational Plasticity in Broadly Neutralizing HIV-1 Antibodies Triggers Polyreactivity.Cell reports · 2018Article
- Repertoire Analysis of Antibody CDR-H3 Loops Suggests Affinity Maturation Does Not Typically Result in Rigidification.Frontiers in immunology · 2018Article
- The Unusual Genetics and Biochemistry of Bovine Immunoglobulins.Advances in immunology · 2018Article
- Therapeutic Antibodies to Ganglioside GD2 Evolved from Highly Selective Germline Antibodies.Cell reports · 2017Article
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The evolution of proteins with novel function is thought to start from precursor proteins that are conformationally heterogeneous. The corresponding genes may be duplicated and then mutated to select and optimize a specific conformation. However, testing this idea has been difficult because of the challenge of quantifying protein flexibility and conformational heterogeneity as a function of evolution. Here, we report the characterization of protein heterogeneity and dynamics as a function of evolution for the antifluorescein antibody 4-4-20. Using nonlinear laser spectroscopy, surface plasmon resonance, and molecular dynamics simulations, we demonstrate that evolution localized the Ab-combining site from a heterogeneous ensemble of conformations to a single conformation by introducing mutations that act cooperatively and over significant distances to rigidify the protein. This study demonstrates how protein dynamics may be tailored by evolution and has important implications for our understanding of how novel protein functions are evolved.
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