7TD5

Structure of human PRC2-EZH1 containing phosphorylated SUZ12

7TD5 の概要

• エントリーDOI: 10.2210/pdb7td5/pdb
• 分子名称: Histone-lysine N-methyltransferase EZH1, Polycomb protein EED, Polycomb protein SUZ12, ... (7 entities in total)
• 機能のキーワード: transcription regulatory complex, histone modification, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 304787.73

構造登録者

Gong, L.,Jiao, L.,Liu, X. (登録日: 2021-12-30, 公開日: 2022-11-16, 最終更新日: 2023-10-18)

主引用文献

Gong, L.,Liu, X.,Jiao, L.,Yang, X.,Lemoff, A.,Liu, X.
CK2-mediated phosphorylation of SUZ12 promotes PRC2 function by stabilizing enzyme active site.
Nat Commun, 13:6781-6781, 2022

PubMed Abstract: Polycomb repressive complex 2 (PRC2) plays a key role in maintaining cell identity during differentiation. Methyltransferase activity of PRC2 on histone H3 lysine 27 is regulated by diverse cellular mechanisms, including posttranslational modification. Here, we report a unique phosphorylation-dependent mechanism stimulating PRC2 enzymatic activity. Residue S583 of SUZ12 is phosphorylated by casein kinase 2 (CK2) in cells. A crystal structure captures phosphorylation in action: the flexible phosphorylation-dependent stimulation loop harboring S583 becomes engaged with the catalytic SET domain through a phosphoserine-centered interaction network, stabilizing the enzyme active site and in particular S-adenosyl-methionine (SAM)-binding pocket. CK2-mediated S583 phosphorylation promotes catalysis by enhancing PRC2 binding to SAM and nucleosomal substrates and facilitates reporter gene repression. Loss of S583 phosphorylation impedes PRC2 recruitment and H3K27me3 deposition in pluripotent mESCs and compromises the ability of PRC2 to maintain differentiated cell identity.

PubMed: 36351927
DOI: 10.1038/s41467-022-34431-1

実験手法

X-RAY DIFFRACTION (2.994 Å)