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TitleStructural basis of human Mediator recruitment by the phosphorylated transcription factor Elk-1.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 3772, Year 2025
Publish dateApr 22, 2025
AuthorsDidier Monté / Zoé Lens / Frédérique Dewitte / Marcus Fislage / Marc Aumercier / Alexis Verger / Vincent Villeret /
PubMed AbstractOne function of Mediator complex subunit MED23 is to mediate transcriptional activation by the phosphorylated transcription factor Elk-1, in response to the Ras-MAPK signaling pathway. Using ...One function of Mediator complex subunit MED23 is to mediate transcriptional activation by the phosphorylated transcription factor Elk-1, in response to the Ras-MAPK signaling pathway. Using cryogenic electron microscopy, we solve a 3.0 Å structure of human MED23 complexed with the phosphorylated activation domain of Elk-1. Elk-1 binds to MED23 via a hydrophobic sequence PSIHFWSTLSP containing one phosphorylated residue (S383), which forms a tight turn around the central Phenylalanine. Binding of Elk-1 induces allosteric changes in MED23 that propagate to the opposite face of the subunit, resulting in the dynamic behavior of a 19-residue segment, which alters the molecular surface of MED23. We design a specific MED23 mutation (G382F) that disrupts Elk--1 binding and consequently impairs Elk-1-dependent serum-induced activation of target genes in the Ras-Raf-MEK-ERK signaling pathway. The structure provides molecular details and insights into a Mediator subunit-transcription factor interface.
External linksNat Commun / PubMed:40263353 / PubMed Central
MethodsEM (single particle)
Resolution2.98 - 3.1 Å
Structure data

50242

9f6y

EMDB-50242, PDB-9f6y:
CryoEM structure of Human Mediator subunit MED23 complexed with phosphorylated Elk-1 transcription factor
Method: EM (single particle) / Resolution: 2.98 Å

50247

9f76

EMDB-50247, PDB-9f76:
CryoEM structure of human Mediator subunit Med23
Method: EM (single particle) / Resolution: 3.1 Å

Source
  • homo sapiens (human)
KeywordsGENE REGULATION / Mediator complex / transcription factor / Med23 / ELK-1 / phosphorylation / TRANSCRIPTION / Mediator / human

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