ArticleCell reports2018
Gcn4-Mediator Specificity Is Mediated by a Large and Dynamic Fuzzy Protein-Protein Complex.
Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed.
- A transcription factor by any other name - function beyond DNA binding and transactivation.EMBO reports · 2026Review
- Nucleosomes and IDRs suppress promiscuous GCN4 binding on minichromosomes.Nature structural & molecular biology · 2026Article
- Current Challenges of Transcription Compartmentalization Research.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Mediator Tail Subunits Hierarchically Couple Transcriptional Condensates to Gene Activation and Genome Organization.bioRxiv : the preprint server for biology · 2026Article
- The Power of Protein Dynamics in Binding and Allostery.Biochemistry · 2026Review
- When MED16 Meets Plant Growth, Development, and Stress Response.International journal of molecular sciences · 2026Review
- Evolutionary turnover of key amino acids explains conservation of function without conservation of sequence in transcriptional activation domains.PLoS genetics · 2026Article
- Disordered but rhythmic-the role of intrinsic protein disorder in eukaryotic circadian timing.FEBS letters · 2026Review
- Sequence and chemical specificity define the functional landscape of intrinsically disordered regions.Nature cell biology · 2026Article
- Phosphorylation-dependent tuning of mRNA deadenylation rates.Nature structural & molecular biology · 2026Article
- A mechanism of synergistic Mediator recruitment in RNA polymerase II transcription activation revealed by single-molecule fluorescence.Molecular cell · 2025Article
- Engineering a serum response factor superactivator of smooth muscle gene expression with a condensate-forming domain.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Insights into Noncanonical and Diversified Functions of ABCF1: From Health to Disease.Journal of molecular biology · 2025Review
- Reconciling competing models on the roles of condensates and soluble complexes in transcription factor function.Molecular cell · 2025Article
- FINCHES: A Computational Framework for Predicting Intermolecular Interactions in Intrinsically Disordered Proteins.International journal of molecular sciences · 2025Review
- The mechanism of YAP/TAZ transactivation and dual targeting for cancer therapy.Nature communications · 2025Article
- Toward universal models for collective interactions in biomolecular condensates.Biophysics reviews · 2025Article
- Boosting transcriptional activities by employing repeated activation domains in transcription factors.The Plant cell · 2025Article
- Fuzzy protein-DNA interactions and beyond: A common theme in transcription?Current opinion in structural biology · 2024Review
- Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Transcription activation domains (ADs) are inherently disordered proteins that often target multiple coactivator complexes, but the specificity of these interactions is not understood. Efficient transcription activation by yeast Gcn4 requires its tandem ADs and four activator-binding domains (ABDs) on its target, the Mediator subunit Med15. Multiple ABDs are a common feature of coactivator complexes. We find that the large Gcn4-Med15 complex is heterogeneous and contains nearly all possible AD-ABD interactions. Gcn4-Med15 forms via a dynamic fuzzy protein-protein interface, where ADs bind the ABDs in multiple orientations via hydrophobic regions that gain helicity. This combinatorial mechanism allows individual low-affinity and specificity interactions to generate a biologically functional, specific, and higher affinity complex despite lacking a defined protein-protein interface. This binding strategy is likely representative of many activators that target multiple coactivators, as it allows great flexibility in combinations of activators that can cooperate to regulate genes with variable coactivator requirements.
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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.