ArticleJournal of molecular biology2012
Construction of a stability landscape of the CH3 domain of human IgG1 by combining directed evolution with high throughput sequencing.
Article in Journal of molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed.
- Multiplexed assays of variant effect for clinical variant interpretation.Nature reviews. Genetics · 2026Review
- Development of a Komagataella phaffii-based expression system for high-activity anti-SARS-CoV-2 neutralizing antibodies.AMB Express · 2025Article
- Article
- Deep Mutational Scanning in Immunology: Techniques and Applications.Pathogens (Basel, Switzerland) · 2025Review
- Exploiting the Fc base of IgG antibodies to create functional nanoparticle conjugates.Scientific reports · 2024Article
- CE-MS/MS and CE-timsTOF to separate and characterize intramolecular disulfide bridges of monoclonal antibody subunits and their application for the assessment of subunit reduction protocols.Analytical and bioanalytical chemistry · 2024Article
- Genotyped functional screening of soluble Fab clones enables in-depth analysis of mutation effects.Scientific reports · 2023Article
- A lentiviral vector B cell gene therapy platform for the delivery of the anti-HIV-1 eCD4-Ig-knob-in-hole-reversed immunoadhesin.Molecular therapy. Methods & clinical development · 2023Article
- Intra-Frontiers in genetics · 2023Article
- Engineering Strategies to Overcome the Stability-Function Trade-Off in Proteins.ACS synthetic biology · 2022Review
- Yeast Surface Display for Protein Engineering: Library Generation, Screening, and Affinity Maturation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Saturation Mutagenesis of the Transmembrane Region of HokC inInternational journal of molecular sciences · 2021Article
- Variant effect predictions capture some aspects of deep mutational scanning experiments.BMC bioinformatics · 2020Article
- MaveDB: an open-source platform to distribute and interpret data from multiplexed assays of variant effect.Genome biology · 2019Article
- Review
- Biophysical Inference of Epistasis and the Effects of Mutations on Protein Stability and Function.Molecular biology and evolution · 2018Article
- Multiplexed assays of variant effects contribute to a growing genotype-phenotype atlas.Human genetics · 2018Review
- Article
- Mutational landscape of antibody variable domains reveals a switch modulating the interdomain conformational dynamics and antigen binding.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Engineering of Fc Fragments with Optimized Physicochemical Properties Implying Improvement of Clinical Potentials for Fc-Based Therapeutics.Frontiers in immunology · 2017Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
One of the most important but still poorly understood issues in protein chemistry is the relationship between sequence and stability of proteins. Here, we present a method for analyzing the influence of each individual residue on the foldability and stability of an entire protein. A randomly mutated library of the crystallizable fragment of human immunoglobulin G class 1 (IgG1-Fc) was expressed on the surface of yeast, followed by heat incubation at 79°C and selection of stable variants that still bound to structurally specific ligands. High throughput sequencing allowed comparison of the mutation rate between the starting and selected library pools, enabling the generation of a stability landscape for the entire CH3 domain of human IgG1 at single residue resolution. Its quality was analyzed with respect to (i) the structure of IgG1-Fc, (ii) evolutionarily conserved positions and (iii) in silico calculations of the energy of unfolding of all variants in comparison with the wild-type protein. In addition, this new experimental approach allowed the assignment of functional epitopes of structurally specific ligands used for selection [Fc γ-receptor I (CD64) and anti-human CH2 domain antibody] to distinct binding regions in the CH2 domain.
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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.