ArticleProceedings of the National Academy of Sciences of the United States of America2020
Designing heterotropically activated allosteric conformational switches using supercharging.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Quantum Defect Sensitization via Phase-Changing Supercharged Antibody Fragments.Journal of the American Chemical Society · 2024Article
- Protein structure-function continuum model: Emerging nexuses between specificity, evolution, and structure.Protein science : a publication of the Protein Society · 2024Review
- Emerging Landscape of Supercharged Proteins and Peptides for Drug Delivery.ACS pharmacology & translational science · 2024Review
- Architectural digest: Thermodynamic stability and domain structure of a consensus monomeric globin.Biophysical journal · 2023Article
- An expandable, modular de novo protein platform for precision redox engineering.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Tailorable Tetrahelical Bundles as a Toolkit for Redox Studies.The journal of physical chemistry. B · 2022Article
- Computational design of a sensitive, selective phase-changing sensor protein for the VX nerve agent.Science advances · 2022Article
- Non-Covalent Coatings on Carbon Nanotubes Mediate Photosensitizer Interactions.ACS applied materials & interfaces · 2021Article
- Recent Progress Using De Novo Design to Study Protein Structure, Design and Binding Interactions.Life (Basel, Switzerland) · 2021Review
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7 authors.
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Abstract
Heterotropic allosteric activation of protein function, in which binding of one ligand thermodynamically activates the binding of another, different ligand or substrate, is a fundamental control mechanism in metabolism and as such has been a long-aspired capability in protein design. Here we show that greatly increasing the magnitude of a protein's net charge using surface supercharging transforms that protein into an allosteric ligand- and counterion-gated conformational molecular switch. To demonstrate this we first modified the designed helical bundle hemoprotein H4, creating a highly charged protein which both unfolds reversibly at low ionic strength and undergoes the ligand-induced folding transition commonly observed in signal transduction by intrinsically disordered proteins in biology. As a result of the high surface-charge density, ligand binding to this protein is allosterically activated up to 1,300-fold by low concentrations of divalent cations and the polyamine spermine. To extend this process further using a natural protein, we similarly modified
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