8F8Z

PHF2 (PHD+JMJ) in Complex with H3 Histone N-Terminal Peptide

Summary for 8F8Z

• Entry DOI: 10.2210/pdb8f8z/pdb
• Descriptor: Lysine-specific demethylase PHF2, H3 N-Terminal Peptide, ZINC ION, ... (6 entities in total)
• Functional Keywords: methyl-lysine binding; aromatic cage; plant homeodomain (phd); jumonji domain; plant homeodomain finger 2 (phf2); histone h3 lysine 4 tri-methylation (h3k4me3), oxidoreductase-transferase complex, oxidoreductase/transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 111043.76

Authors

Horton, J.R.,Cheng, X. (deposition date: 2022-11-22, release date: 2023-01-18, Last modification date: 2023-02-08)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.3 Å)