8F8Y

PHF2 (PHD+JMJ) in Complex with VRK1 N-Terminal Peptide

8F8Y の概要

• エントリーDOI: 10.2210/pdb8f8y/pdb
• 分子名称: Lysine-specific demethylase PHF2, Serine/threonine-protein kinase VRK1 N-terminus peptide, ZINC ION, ... (6 entities in total)
• 機能のキーワード: methyl-lysine binding, aromatic cage, plant homeodomain, phd, jumonji domain, plant homeodomain finger 2, phf2, histone h3 lysine 4 tri-methylation, h3k4me3, protein binding, oxidoreductase-transferase complex, oxidoreductase/transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 108598.67

構造登録者

Horton, J.R.,Cheng, X. (登録日: 2022-11-22, 公開日: 2023-01-18, 最終更新日: 2023-02-08)

主引用文献

Horton, J.R.,Zhou, J.,Chen, Q.,Zhang, X.,Bedford, M.T.,Cheng, X.
A complete methyl-lysine binding aromatic cage constructed by two domains of PHF2.
J.Biol.Chem., 299:102862-102862, 2022

PubMed Abstract: The N-terminal half of PHF2 harbors both a plant homeodomain (PHD) and a Jumonji domain. The PHD recognizes both histone H3 trimethylated at lysine 4 and methylated nonhistone proteins including vaccinia-related kinase 1 (VRK1). The Jumonji domain erases the repressive dimethylation mark from histone H3 lysine 9 (H3K9me2) at select promoters. The N-terminal amino acid sequences of H3 (ARTK) and VRK1 (PRVK) bear an arginine at position 2 and lysine at position 4. Here, we show that the PHF2 N-terminal half binds to H3 and VRK1 peptides containing K4me3, with dissociation constants (K values) of 160 nM and 42 nM, respectively, which are 4 × and 21 × lower (and higher affinities) than for the isolated PHD domain of PHF2. X-ray crystallography revealed that the K4me3-containing peptide is positioned within the PHD and Jumonji interface, with the positively charged R2 residue engaging acidic residues of the PHD and Jumonji domains and with the K4me3 moiety encircled by aromatic residues from both domains. We suggest that the micromolar binding affinities commonly observed for isolated methyl-lysine reader domains could be improved via additional functional interactions within the same polypeptide or its binding partners.

PubMed: 36596360
DOI: 10.1016/j.jbc.2022.102862

実験手法

X-RAY DIFFRACTION (3.06 Å)