ArticleNature communications2021
Epistasis shapes the fitness landscape of an allosteric specificity switch.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Network analysis of correlated conformational dynamics across the evolution of influenza A virus NS1.bioRxiv : the preprint server for biology · 2026Article
- From sites to structure to serology: a roadmap for structure-aware molecular evolution of antigenically evolving viruses.Journal of virology · 2026Review
- Selective control of ligand binding through a distal mutation that alters the protein native ensemble.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Conserved Motifs in the Ligand-Binding Domain of TetR Family Regulators: Identification and Analysis.Computational and structural biotechnology journal · 2026Article
- Identification and understanding of allostery hotspots in proteins: Integration of deep mutational scanning and multi-faceted computational analyses.Journal of molecular biology · 2025Review
- Engineered TtgR-Based Whole-Cell Biosensors for Quantitative and Selective Monitoring of Bioactive Compounds.Biosensors · 2025Article
- Evolutionary rewiring of the dynamic network underpinning allosteric epistasis in NS1 of the influenza A virus.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Tailoring industrial enzymes for thermostability and activity evolution by the machine learning-based iCASE strategy.Nature communications · 2025Article
- Bioengineering hybrid artificial life.Frontiers in bioinformatics · 2025Review
- Optimizing enzyme thermostability by combining multiple mutations using protein language model.mLife · 2024Article
- Evolutionary insights into the stereoselectivity of imine reductases based on ancestral sequence reconstruction.Nature communications · 2024Article
- Highly multiplexed design of an allosteric transcription factor to sense new ligands.Nature communications · 2024Article
- Specialization Restricts the Evolutionary Paths Available to Yeast Sugar Transporters.Molecular biology and evolution · 2024Article
- Specialization restricts the evolutionary paths available to yeast sugar transporters.bioRxiv : the preprint server for biology · 2024Article
- Highly multiplexed design of an allosteric transcription factor to sense novel ligands.bioRxiv : the preprint server for biology · 2024Article
- Rheostats, toggles, and neutrals, Oh my! A new framework for understanding how amino acid changes modulate protein function.The Journal of biological chemistry · 2024Review
- Advances in ligand-specific biosensing for structurally similar molecules.Cell systems · 2023Review
- Exploring and Learning the Universe of Protein Allostery Using Artificial Intelligence Augmented Biophysical and Computational Approaches.Journal of chemical information and modeling · 2023Review
- Probing conformational landscapes and mechanisms of allosteric communication in the functional states of the ABL kinase domain using multiscale simulations and network-based mutational profiling of allosteric residue potentials.The Journal of chemical physics · 2022Article
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Authors and funding
5 authors.
Funding
Abstract
Epistasis is a major determinant in the emergence of novel protein function. In allosteric proteins, direct interactions between inducer-binding mutations propagate through the allosteric network, manifesting as epistasis at the level of biological function. Elucidating this relationship between local interactions and their global effects is essential to understanding evolution of allosteric proteins. We integrate computational design, structural and biophysical analysis to characterize the emergence of novel inducer specificity in an allosteric transcription factor. Adaptive landscapes of different inducers of the designed mutant show that a few strong epistatic interactions constrain the number of viable sequence pathways, revealing ridges in the fitness landscape leading to new specificity. The structure of the designed mutant shows that a striking change in inducer orientation still retains allosteric function. Comparing biophysical and functional properties suggests a nonlinear relationship between inducer binding affinity and allostery. Our results highlight the functional and evolutionary complexity of allosteric proteins.
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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.