5TQR

ctPRC2 in an autoinhibited conformation bound to S-adenosylmethionine

Summary for 5TQR

• Entry DOI: 10.2210/pdb5tqr/pdb
• Related: 5BJS 5VK3
• Descriptor: Polycomb Protein EED, Histone-lysine N-methyltransferase EZH2, Polycomb protein SUZ12, ZINC ION, ... (5 entities in total)
• Functional Keywords: transferase
• Biological source: Chaetomium thermophilum; More
• Total number of polymer chains: 2
• Total formula weight: 173812.68

Authors

Bratkowski, M.A.,Liu, X. (deposition date: 2016-10-24, release date: 2017-06-14, Last modification date: 2023-10-04)

Primary citation

Bratkowski, M.,Yang, X.,Liu, X.
Polycomb repressive complex 2 in an autoinhibited state.
J. Biol. Chem., 292:13323-13332, 2017

PubMed Abstract: Polycomb-group proteins control many fundamental biological processes, such as anatomical development in mammals and vernalization in plants. Polycomb repressive complex 2 (PRC2) is responsible for methylation of histone H3 lysine 27 (H3K27), and trimethylated H3K27 (H3K27me3) is implicated in epigenetic gene silencing. Recent genomic, biochemical, and structural data indicate that PRC2 is broadly conserved from yeast to human in many aspects. Here, we determined the crystal structure of an apo-PRC2 from the fungus captured in a autoinhibited state, which represents a novel conformation of PRC2 associated with enzyme regulation in light of the basal and stimulated states that we reported previously. We found that binding by the cofactor -adenosylmethionine mitigates this autoinhibited structural state. Using steady-state enzyme kinetics, we also demonstrated that disrupting the autoinhibition results in a vastly activated enzyme complex. Autoinhibition provides a novel structural platform that may enable control of PRC2 activity in response to diverse transcriptional states and chromatin contexts and set a ground state to allow PRC2 activation by other cellular mechanisms as well.

PubMed: 28607149
DOI: 10.1074/jbc.M117.787572

Experimental method

X-RAY DIFFRACTION (2.571 Å)