Evidence map›Paper›PMID 29562181›Full record

ArticleCell reports2018

Gcn4-Mediator Specificity Is Mediated by a Large and Dynamic Fuzzy Protein-Protein Complex.

Lisa M Tuttle, Derek Pacheco, Linda Warfield, Jie Luo, Jeff Ranish, Steven Hahn, Rachel E Klevit

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

85 citing papers in PubMed.

  1. Review
  2. Article
  3. Current Challenges of Transcription Compartmentalization Research.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  4. Article
  5. Review
  6. When MED16 Meets Plant Growth, Development, and Stress Response.International journal of molecular sciences · 2026
    Review
  7. Article
  8. Review
  9. Article
  10. Phosphorylation-dependent tuning of mRNA deadenylation rates.Nature structural & molecular biology · 2026
    Article
  11. Article
  12. 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 · 2025
    Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

25 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Lisa M TuttleDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Derek PachecoDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Linda WarfieldDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Jie LuoThe Institute for Systems Biology, Seattle, WA 98109, USA.
Jeff RanishThe Institute for Systems Biology, Seattle, WA 98109, USA.
Steven HahnDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Electronic address: shahn@fredhutch.org.
Rachel E KlevitDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA. Electronic address: klevit@u.washington.edu.

Funding

Quantitative Systems BiologyP50GM076547 · NIGMS · INSTITUTE FOR SYSTEMS BIOLOGY · PI BALIGA, NITIN S · 2006 to 2016
$30.6M
Mechanisms of eukaryotic transcription activationR01GM075114 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI HAHN, STEVEN M · 2005 to 2020
$7.9M
TFIIH and Transcription RegulationR01GM110064 · NIGMS · UNIVERSITY OF COLORADO · PI RANISH, JEFFREY A, TAATJES, DYLAN J · 2016 to 2019
$2.2M
NIGMS NIH HHS P50 GM076547NIGMS NIH HHS R01 GM075114NIGMS NIH HHS R01 GM110064
6 · The paper itself

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.

Indexed as

Basic-Leucine Zipper Transcription FactorsMediator ComplexMembrane ProteinsProtein DomainsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTranscriptional ActivationBasic-Leucine Zipper Transcription FactorsGAL11 protein, S cerevisiaeGCN4 protein, S cerevisiaeMediator ComplexMembrane ProteinsSaccharomyces cerevisiae Proteinsfuzzy bindingintrinsically disordered proteinstranscription activation

Identifiers

PMID29562181
PMCPMC5908246

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Registered trials

None linked

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.