Mediator subunit Med15 dictates the conserved "fuzzy" binding mechanism of yeast transcription activators Gal4 and Gcn4.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
13 04 2021
Historique:
received: 14 11 2019
accepted: 11 03 2021
entrez: 14 4 2021
pubmed: 15 4 2021
medline: 29 4 2021
Statut: epublish

Résumé

The acidic activation domain (AD) of yeast transcription factor Gal4 plays a dual role in transcription repression and activation through binding to Gal80 repressor and Mediator subunit Med15. The activation function of Gal4 arises from two hydrophobic regions within the 40-residue AD. We show by NMR that each AD region binds the Mediator subunit Med15 using a "fuzzy" protein interface. Remarkably, comparison of chemical shift perturbations shows that Gal4 and Gcn4, two intrinsically disordered ADs of different sequence, interact nearly identically with Med15. The finding that two ADs of different sequence use an identical fuzzy binding mechanism shows a common sequence-independent mechanism for AD-Mediator binding, similar to interactions within a hydrophobic cloud. In contrast, the same region of Gal4 AD interacts strongly with Gal80 via a distinct structured complex, implying that the structured binding partner of an intrinsically disordered protein dictates the type of protein-protein interaction.

Identifiants

pubmed: 33850123
doi: 10.1038/s41467-021-22441-4
pii: 10.1038/s41467-021-22441-4
pmc: PMC8044209
doi:

Substances chimiques

Basic-Leucine Zipper Transcription Factors 0
DNA-Binding Proteins 0
GAL11 protein, S cerevisiae 0
GAL4 protein, S cerevisiae 0
GAL80 protein, S cerevisiae 0
GCN4 protein, S cerevisiae 0
Mediator Complex 0
Repressor Proteins 0
Saccharomyces cerevisiae Proteins 0
Transcription Factors 0
Methyltransferases EC 2.1.1.-
mRNA (guanine(N7))-methyltransferase EC 2.1.1.56

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

2220

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM075114
Pays : United States

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Auteurs

Lisa M Tuttle (LM)

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Department of Biochemistry, University of Washington, Seattle, WA, USA.

Derek Pacheco (D)

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Inventprise LLC, Redmond, WA, USA.

Linda Warfield (L)

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Damien B Wilburn (DB)

Department of Genome Sciences, University of Washington, Seattle, WA, USA.

Steven Hahn (S)

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. shahn@fredhutch.org.

Rachel E Klevit (RE)

Department of Biochemistry, University of Washington, Seattle, WA, USA. klevit@u.washington.edu.

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Classifications MeSH