ArticleNature communications2024
The genetic architecture of protein interaction affinity and specificity.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed.
- Variant characterization in the intrinsically disordered human proteome.Nature structural & molecular biology · 2026Article
- Human genetics across levels of biological organization.Nature reviews. Genetics · 2026Review
- Free energy perturbations in enzyme kinetic models reveal cryptic epistasis.PLoS computational biology · 2026Article
- Interrelational Proteomic Sequence Features Enhance Predictive Modeling: Application to COVID-19 Severity.Biomedicines · 2026Article
- Mapping the Functional Landscape ofmedRxiv : the preprint server for health sciences · 2025Article
- Epistatic drift in protein evolution.Current opinion in genetics & development · 2025Review
- Article
- Employing deep mutational scanning in theProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Highly replicated experiments studying complex genotypes using nested DNA barcodes.G3 (Bethesda, Md.) · 2025Article
- Computational and experimental discovery of peptide inhibitors targeting survivin for therapeutic potential in cancer.Scientific reports · 2025Article
- Engineering Protein-Polyelectrolyte Interactions for Cellular Applications.Annual review of chemical and biomolecular engineering · 2025Review
- Experimental approaches to investigate biophysical interactions between homeodomain transcription factors and DNA.Biochimica et biophysica acta. Gene regulatory mechanisms · 2025Review
- Article
- Optimization of a deep mutational scanning workflow to improve quantification of mutation effects on protein-protein interactions.BMC genomics · 2024Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
The encoding and evolution of specificity and affinity in protein-protein interactions is poorly understood. Here, we address this question by quantifying how all mutations in one protein, JUN, alter binding to all other members of a protein family, the 54 human basic leucine zipper transcription factors. We fit a global thermodynamic model to the data to reveal that most affinity changing mutations equally affect JUN's affinity to all its interaction partners. Mutations that alter binding specificity are relatively rare but distributed throughout the interaction interface. Specificity is determined both by features that promote on-target interactions and by those that prevent off-target interactions. Approximately half of the specificity-defining residues in JUN contribute both to promoting on-target binding and preventing off-target binding. Nearly all specificity-altering mutations in the interaction interface are pleiotropic, also altering affinity to all partners. In contrast, mutations outside the interface can tune global affinity without affecting specificity. Our results reveal the distributed encoding of specificity and affinity in an interaction interface and how coiled-coils provide an elegant solution to the challenge of optimizing both specificity and affinity in a large protein family.
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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 Socratic graph.