ArticleProceedings of the National Academy of Sciences of the United States of America2020
Unexpected specificity within dynamic transcriptional protein-protein complexes.
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 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Sequence and chemical specificity define the functional landscape of intrinsically disordered regions.Nature cell biology · 2026Article
- Article
- A dual interaction between RSV NS1 and MED25 ACID domain reshapes antiviral responses.PLoS pathogens · 2025Article
- Short activation domains control chromatin association of transcription factors.bioRxiv : the preprint server for biology · 2025Article
- A Lipopeptidomimetic of Transcriptional Activation Domains Selectively Disrupts the Coactivator Med25 Protein-Protein Interactions.Angewandte Chemie (International ed. in English) · 2024Article
- Commonly asked questions about transcriptional activation domains.Current opinion in structural biology · 2024Review
- Molecular switching in transcription through splicing and proline-isomerization regulates stress responses in plants.Nature communications · 2024Article
- Inhibition of CREB Binding and Function with a Dual-Targeting Ligand.Biochemistry · 2024Article
- General Theory of Specific Binding: Insights from a Genetic-Mechano-Chemical Protein Model.Molecular biology and evolution · 2022Article
- The Mediator complex as a master regulator of transcription by RNA polymerase II.Nature reviews. Molecular cell biology · 2022Review
- αα-hub coregulator structure and flexibility determine transcription factor binding and selection in regulatory interactomes.The Journal of biological chemistry · 2022Article
- Understanding p300-transcription factor interactions using sequence variation and hybridization.RSC chemical biology · 2022Article
- Transcription Factor Dynamics.Cold Spring Harbor perspectives in biology · 2021Review
- Advances in targeting 'undruggable' transcription factors with small molecules.Nature reviews. Drug discovery · 2021Review
- Unifying Catalysis Framework to Dissect Proteasomal Degradation Paradigms.ACS central science · 2021Review
- Everything at once: cryo-EM yields remarkable insights into human RNA polymerase II transcription.Nature structural & molecular biology · 2021Article
- Norstictic Acid Is a Selective Allosteric Transcriptional Regulator.Journal of the American Chemical Society · 2021Article
- Mediator subunit Med15 dictates the conserved "fuzzy" binding mechanism of yeast transcription activators Gal4 and Gcn4.Nature communications · 2021Article
- Inhibition of Nonfunctional Ras.Cell chemical biology · 2021Review
- Drugging Fuzzy Complexes in Transcription.Frontiers in molecular biosciences · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
A key functional event in eukaryotic gene activation is the formation of dynamic protein-protein interaction networks between transcriptional activators and transcriptional coactivators. Seemingly incongruent with the tight regulation of transcription, many biochemical and biophysical studies suggest that activators use nonspecific hydrophobic and/or electrostatic interactions to bind to coactivators, with few if any specific contacts. Here a mechanistic dissection of a set of representative dynamic activator•coactivator complexes, comprised of the ETV/PEA3 family of activators and the coactivator Med25, reveals a different molecular recognition model. The data demonstrate that small sequence variations within an activator family significantly redistribute the conformational ensemble of the complex while not affecting overall affinity, and distal residues within the activator-not often considered as contributing to binding-play a key role in mediating conformational redistribution. The ETV/PEA3•Med25 ensembles are directed by specific contacts between the disordered activator and the Med25 interface, which is facilitated by structural shifts of the coactivator binding surface. Taken together, these data highlight the critical role coactivator plasticity plays in recognition of disordered activators and indicate that molecular recognition models of disordered proteins must consider the ability of the binding partners to mediate specificity.
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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.