9F76

CryoEM structure of human Mediator subunit Med23

9F76 の概要

• エントリーDOI: 10.2210/pdb9f76/pdb
• EMDBエントリー: 50247
• 分子名称: Mediator of RNA polymerase II transcription subunit 23 (1 entity in total)
• 機能のキーワード: mediator, med23, transcription, human
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 158294.89

構造登録者

Monte, D.,Verger, A.,Lens, Z.,Villeret, V. (登録日: 2024-05-03, 公開日: 2025-04-30)

主引用文献

Monte, D.,Lens, Z.,Dewitte, F.,Fislage, M.,Aumercier, M.,Verger, A.,Villeret, V.
Structural basis of human Mediator recruitment by the phosphorylated transcription factor Elk-1.
Nat Commun, 16:3772-3772, 2025

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 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.

PubMed: 40263353
DOI: 10.1038/s41467-025-59014-8

実験手法

ELECTRON MICROSCOPY (3.1 Å)