6V3Y

Crystal structure of EED in complex with PALI1-K1219me3 peptide

6V3Y の概要

• エントリーDOI: 10.2210/pdb6v3y/pdb
• 分子名称: Polycomb protein EED, PALI1 peptide (3 entities in total)
• 機能のキーワード: eed, pali1, tri-methyl-lysine, lcor, c10orf12, gene regulation
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 42039.80

構造登録者

Zhang, Q.,Davidovich, C. (登録日: 2019-11-26, 公開日: 2021-05-26, 最終更新日: 2023-10-11)

主引用文献

Zhang, Q.,Agius, S.C.,Flanigan, S.F.,Uckelmann, M.,Levina, V.,Owen, B.M.,Davidovich, C.
PALI1 facilitates DNA and nucleosome binding by PRC2 and triggers an allosteric activation of catalysis.
Nat Commun, 12:4592-4592, 2021

PubMed Abstract: The polycomb repressive complex 2 (PRC2) is a histone methyltransferase that maintains cell identities. JARID2 is the only accessory subunit of PRC2 that known to trigger an allosteric activation of methyltransferase. Yet, this mechanism cannot be generalised to all PRC2 variants as, in vertebrates, JARID2 is mutually exclusive with most of the accessory subunits of PRC2. Here we provide functional and structural evidence that the vertebrate-specific PRC2 accessory subunit PALI1 emerged through a convergent evolution to mimic JARID2 at the molecular level. Mechanistically, PRC2 methylates PALI1 K1241, which then binds to the PRC2-regulatory subunit EED to allosterically activate PRC2. PALI1 K1241 is methylated in mouse and human cell lines and is essential for PALI1-induced allosteric activation of PRC2. High-resolution crystal structures revealed that PALI1 mimics the regulatory interactions formed between JARID2 and EED. Independently, PALI1 also facilitates DNA and nucleosome binding by PRC2. In acute myelogenous leukemia cells, overexpression of PALI1 leads to cell differentiation, with the phenotype altered by a separation-of-function PALI1 mutation, defective in allosteric activation and active in DNA binding. Collectively, we show that PALI1 facilitates catalysis and substrate binding by PRC2 and provide evidence that subunit-induced allosteric activation is a general property of holo-PRC2 complexes.

PubMed: 34321472
DOI: 10.1038/s41467-021-24866-3

実験手法

X-RAY DIFFRACTION (1.63 Å)