7td5

Structure of human PRC2-EZH1 containing phosphorylated SUZ12Structure of human PRC2-EZH1 containing phosphorylated SUZ12

Structural highlights

7td5 is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.994Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

EZH1_HUMAN Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH1 complex, which methylates 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Required for embryonic stem cell derivation and self-renewal, suggesting that it is involved in safeguarding embryonic stem cell identity. Compared to EZH2-containing complexes, it is less abundant in embryonic stem cells, has weak methyltransferase activity and plays a less critical role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation.^[1]

Publication Abstract from PubMed

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.

CK2-mediated phosphorylation of SUZ12 promotes PRC2 function by stabilizing enzyme active site.,Gong L, Liu X, Jiao L, Yang X, Lemoff A, Liu X Nat Commun. 2022 Nov 9;13(1):6781. doi: 10.1038/s41467-022-34431-1. PMID:36351927^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Margueron R, Li G, Sarma K, Blais A, Zavadil J, Woodcock CL, Dynlacht BD, Reinberg D. Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms. Mol Cell. 2008 Nov 21;32(4):503-18. doi: 10.1016/j.molcel.2008.11.004. PMID:19026781 doi:http://dx.doi.org/10.1016/j.molcel.2008.11.004
↑ 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. 2022 Nov 9;13(1):6781. doi: 10.1038/s41467-022-34431-1. PMID:36351927 doi:http://dx.doi.org/10.1038/s41467-022-34431-1

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OCA

[1] Margueron R, Li G, Sarma K, Blais A, Zavadil J, Woodcock CL, Dynlacht BD, Reinberg D. Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms. Mol Cell. 2008 Nov 21;32(4):503-18. doi: 10.1016/j.molcel.2008.11.004. PMID:19026781 doi:http://dx.doi.org/10.1016/j.molcel.2008.11.004

[2] 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. 2022 Nov 9;13(1):6781. doi: 10.1038/s41467-022-34431-1. PMID:36351927 doi:http://dx.doi.org/10.1038/s41467-022-34431-1

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