ArticleProceedings of the National Academy of Sciences of the United States of America2012
Agonism/antagonism switching in allosteric ensembles.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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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
54 citing papers in PubMed.
- Long-term tamoxifen impacts the ovary but not preimplantation embryo development†.Biology of reproduction · 2026Article
- Second-order allosteric control as a mechanism for compensatory mutations in B-cell translocation gene 2.Protein science : a publication of the Protein Society · 2025Article
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- Protein structure-function continuum model: Emerging nexuses between specificity, evolution, and structure.Protein science : a publication of the Protein Society · 2024Review
- KCNT2-Related Disorders: Phenotypes, Functional, and Pharmacological Properties.Annals of neurology · 2023Article
- Deep mining of the protein energy landscape.Structural dynamics (Melville, N.Y.) · 2023Article
- Leaderless secretory proteins of the neurodegenerative diseases via TNTs: a structure-function perspective.Frontiers in molecular neuroscience · 2023Review
- Allostery in the dynamic coactivator domain KIX occurs through minor conformational micro-states.PLoS computational biology · 2022Article
- Drugging the Undruggable: Targeting the N-Terminal Domain of Nuclear Hormone Receptors.Advances in experimental medicine and biology · 2022Article
- State-selective frustration as a key driver of allosteric pluripotency.Chemical science · 2021Article
- Article
- Tumor Susceptibility Gene 101 Regulates the Glucocorticoid Receptor through Disorder-Mediated Allostery.Biochemistry · 2021Article
- Dynamic allosteric communication pathway directing differential activation of the glucocorticoid receptor.Science advances · 2020Article
- Allosteric pluripotency as revealed by protein kinase A.Science advances · 2020Article
- Dissecting the Functional Contributions of the Intrinsically Disordered C-terminal Tail of Bacillus subtilis FtsZ.Journal of molecular biology · 2020Article
- Allosteric inhibition explained through conformational ensembles sampling distinct "mixed" states.Computational and structural biotechnology journal · 2020Review
- Entropy and Information within Intrinsically Disordered Protein Regions.Entropy (Basel, Switzerland) · 2019Article
- Domain insertion permissibility-guided engineering of allostery in ion channels.Nature communications · 2019Article
- A comprehensive ensemble model for comparing the allosteric effect of ordered and disordered proteins.PLoS computational biology · 2018Article
- Expanding the Paradigm: Intrinsically Disordered Proteins and Allosteric Regulation.Journal of molecular biology · 2018Review
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Ligands for several transcription factors can act as agonists under some conditions and antagonists under others. The structural and molecular bases of such effects are unknown. Previously, we demonstrated how the folding of intrinsically disordered (ID) protein sequences, in particular, and population shifts, in general, could be used to mediate allosteric coupling between different functional domains, a model that has subsequently been validated in several systems. Here it is shown that population redistribution within allosteric systems can be used as a mechanism to tune protein ensembles such that a given ligand can act as both an agonist and an antagonist. Importantly, this mechanism can be robustly encoded in the ensemble, and does not require that the interactions between the ligand and the protein differ when it is acting either as an agonist or an antagonist. Instead, the effect is due to the relative probabilities of states prior to the addition of the ligand. The ensemble view of allostery that is illuminated by these studies suggests that rather than being seen as switches with fixed responses to allosteric activation, ensembles can evolve to be "functionally pluripotent," with the capacity to up or down regulate activity in response to a stimulus. This result not only helps to explain the prevalence of intrinsic disorder in transcription factors and other cell signaling proteins, it provides important insights about the energetic ground rules governing site-to-site communication in all allosteric systems.
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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.