7d87 | pdb_00007d87

Crystal Structure of zebrafish PHF14-PZP in complex with H3(1-25)

spinqualitylabelsall models 7d87, resolution 2.11Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7d87 is a 2 chain structure with sequence from Danio rerio and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.11Å Ligands: CA, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PHF14_DANRE Histone-binding protein (PubMed:34365506). Binds preferentially to unmodified histone H3 but can also bind to a lesser extent to histone H3 trimethylated at 'Lys-9' (H3K9me3) as well as to histone H3 monomethylated at 'Lys-27' (H3K27ac) and trimethylated at 'Lys-27' (H3K27me3) (PubMed:34365506). Represses PDGFRA expression, thus playing a role in regulation of mesenchymal cell proliferation (By similarity).[UniProtKB:Q9D4H9] Publication Abstract from PubMed Histone recognition constitutes a key epigenetic mechanism in gene regulation and cell fate decision. PHF14 is a conserved multi-PHD finger protein that has been implicated in organ development, tissue homeostasis, and tumorigenesis. Here we show that PHF14 reads unmodified histone H3(1-34) through an integrated PHD1-ZnK-PHD2 cassette (PHF14PZP). Our binding, structural and HDX-MS analyses revealed a feature of bipartite recognition, in which PHF14PZP utilizes two distinct surfaces for concurrent yet separable engagement of segments H3-Nter (e.g. 1-15) and H3-middle (e.g. 14-34) of H3(1-34). Structural studies revealed a novel histone H3 binding mode by PHD1 of PHF14PZP, in which a PHF14-unique insertion loop but not the core beta-strands of a PHD finger dominates H3K4 readout. Binding studies showed that H3-PHF14PZP engagement is sensitive to modifications occurring to H3 R2, T3, K4, R8 and K23 but not K9 and K27, suggesting multiple layers of modification switch. Collectively, our work calls attention to PHF14 as a 'ground' state (unmodified) H3(1-34) reader that can be negatively regulated by active marks, thus providing molecular insights into a repressive function of PHF14 and its derepression. Molecular basis for bipartite recognition of histone H3 by the PZP domain of PHF14.,Zheng S, Bi Y, Chen H, Gong B, Jia S, Li H Nucleic Acids Res. 2021 Sep 7;49(15):8961-8973. doi: 10.1093/nar/gkab670. PMID:34365506 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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