7TD5

Structure of human PRC2-EZH1 containing phosphorylated SUZ12

Summary for 7TD5

• Entry DOI: 10.2210/pdb7td5/pdb
• Descriptor: Histone-lysine N-methyltransferase EZH1, Polycomb protein EED, Polycomb protein SUZ12, ... (7 entities in total)
• Functional Keywords: transcription regulatory complex, histone modification, transcription
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 10
• Total formula weight: 304787.73

Authors

Gong, L.,Jiao, L.,Liu, X. (deposition date: 2021-12-30, release date: 2022-11-16, Last modification date: 2023-10-18)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.994 Å)