3K26

Complex structure of EED and trimethylated H3K4

3K26 の概要

• エントリーDOI: 10.2210/pdb3k26/pdb
• 関連するPDBエントリー: 3JPX 3JZG 3JZH 3JZN 3K27
• 分子名称: Polycomb protein EED, HISTONE PEPTIDE (3 entities in total)
• 機能のキーワード: wd40, structural genomics, nppsfa, national project on protein structural and functional analysis, structural genomics consortium, sgc, alternative initiation, chromatin regulator, nucleus, phosphoprotein, repressor, transcription, transcription regulation, wd repeat, gene regulation, national project on protein structural and functional analyses
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: O75530
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 43721.89

構造登録者

Bian, C.B.,Xu, C.,Qiu, W.,Bountra, C.,Weigelt, J.,Arrowsmith, C.H.,Edwards, A.M.,Bochkarev, A.,Min, J.,Structural Genomics Consortium (SGC) (登録日: 2009-09-29, 公開日: 2009-12-15, 最終更新日: 2025-03-26)

主引用文献

Xu, C.,Bian, C.,Yang, W.,Galka, M.,Ouyang, H.,Chen, C.,Qiu, W.,Liu, H.,Jones, A.E.,Mackenzie, F.,Pan, P.,Li, S.S.,Wang, H.,Min, J.
Binding of different histone marks differentially regulates the activity and specificity of polycomb repressive complex 2 (PRC2).
Proc.Natl.Acad.Sci.USA, 107:19266-19271, 2010

PubMed Abstract: The polycomb repressive complex 2 (PRC2) is the major methyltransferase for H3K27 methylation, a modification critical for maintaining repressed gene expression programs throughout development. It has been previously shown that PRC2 maintains histone methylation patterns during DNA replication in part through its ability to bind to H3K27me3. However, the mechanism by which PRC2 recognizes H3K27me3 is unclear. Here we show that the WD40 domain of EED, a PRC2 component, is a methyllysine histone-binding domain. The crystal structures of apo-EED and EED in complex respectively with five different trimethyllysine histone peptides reveal that EED binds these peptides via the top face of its β-propeller architecture. The ammonium group of the trimethyllysine is accommodated by an aromatic cage formed by three aromatic residues, while its aliphatic chain is flanked by a fourth aromatic residue. Our structural data provide an explanation for the preferential recognition of the Ala-Arg-Lys-Ser motif-containing trimethylated H3K27, H3K9, and H1K26 marks by EED over lower methylation states and other histone methyllysine marks. More importantly, we found that binding of different histone marks by EED differentially regulates the activity and specificity of PRC2. Whereas the H3K27me3 mark stimulates the histone methyltransferase activity of PRC2, the H1K26me3 mark inhibits PRC2 methyltransferase activity on the nucleosome. Moreover, H1K26me3 binding switches the specificity of PRC2 from methylating H3K27 to EED. In addition to determining the molecular basis of EED-methyllysine recognition, our work provides the biochemical characterization of how the activity of a histone methyltransferase is oppositely regulated by two histone marks.

PubMed: 20974918
DOI: 10.1073/pnas.1008937107

実験手法

X-RAY DIFFRACTION (1.58 Å)