9f76
From Proteopedia
CryoEM structure of human Mediator subunit Med23
Structural highlights
DiseaseMED23_HUMAN Autosomal recessive non-syndromic intellectual disability. The disease is caused by mutations affecting the gene represented in this entry. FunctionMED23_HUMAN Required for transcriptional activation subsequent to the assembly of the pre-initiation complex (By similarity). Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors. Required for transcriptional activation by adenovirus E1A protein. Required for ELK1-dependent transcriptional activation in response to activated Ras signaling.[1] [2] [3] Publication Abstract from PubMedOne 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 A 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. Structural basis of human Mediator recruitment by the phosphorylated transcription factor Elk-1.,Monte D, Lens Z, Dewitte F, Fislage M, Aumercier M, Verger A, Villeret V Nat Commun. 2025 Apr 22;16(1):3772. doi: 10.1038/s41467-025-59014-8. PMID:40263353[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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