9F76 | pdb_00009f76

Structural basis of human Mediator recruitment by the phosphorylated transcription factor Elk-1.

(2025) Nat Commun 16: 3772-3772

• PubMed: 40263353 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1038/s41467-025-59014-8
• Primary Citation of Related Structures:  
  9F6Y, 9F76


• PubMed Abstract: 
  

  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?? structure of human MED23 complexed with the phosphorylated activation domain of Elk-1. Elk-1 binds to MED23 via a hydrophobic sequence PSIHFWSTLS ^P P containing one phosphorylated residue (S383 ^p ), 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.

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Organizational Affiliation: 

CNRS EMR 9002 Integrative Structural Biology, Inserm U 1167 - RID-AGE, Univ. Lille, CHU Lille, Institut Pasteur de Lille, Lille, France. Didier.Monte@univ-lille.fr.