4R7A

Crystal Structure of RBBP4 bound to PHF6 peptide

4R7A の概要

• エントリーDOI: 10.2210/pdb4r7a/pdb
• 分子名称: PHD finger protein 6, Histone-binding protein RBBP4, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: wd40 repeat domain, gene regulation, nuclear
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: Q8IWS0 Q09028
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49609.82

構造登録者

Liu, Z.,Li, F.,Zhang, B.,Li, S.,Wu, J.,Shi, Y. (登録日: 2014-08-27, 公開日: 2015-01-14, 最終更新日: 2023-11-08)

主引用文献

Liu, Z.,Li, F.,Zhang, B.,Li, S.,Wu, J.,Shi, Y.
Structural Basis of Plant Homeodomain Finger 6 (PHF6) Recognition by the Retinoblastoma Binding Protein 4 (RBBP4) Component of the Nucleosome Remodeling and Deacetylase (NuRD) Complex
J.Biol.Chem., 290:6630-6638, 2015

PubMed Abstract: The NuRD complex is a conserved transcriptional coregulator that contains both chromatin-remodeling and histone deacetylase activities. Mutations of PHF6 are found in patients with Börjeson-Forssman-Lehmann syndrome, T-cell acute lymphoblastic leukemia, or acute myeloid leukemia. Recently, PHF6 was identified to interact with the NuRD complex, and this interaction is mediated by the RBBP4 component. However, little is known about the molecular basis for the interaction. Here, we present the crystal structure of the complex of the NuRD subunit RBBP4 bound to the PHF6 peptide (residues 162-170). The PHF6 peptide binds to the top surface of the RBBP4 β-propeller. A pair of positively charged residues of the PHF6 peptide insert into the negatively charged pocket of RBBP4, which is critical for the interaction between PHF6 and RBBP4. Corresponding PHF6 mutants impair this interaction in vitro and in vivo. Structural comparison shows that the PHF6-binding pocket overlaps with FOG1 and histone H3 on RBBP4/Nurf55, but it is distinct from the pocket recognizing histone H4, Su(z)12, and MTA1. We further show that the middle disordered region (residues 145-207, containing the RBBP4-binding motif) is sufficient for the transcriptional repression mediated by PHF6 on the GAL4 reporter, and knockdown of RBBP4 diminished the PHF6-mediated repression. Our RBBP4-PHF6 complex structure provides insights into the molecular basis of PHF6-NuRD complex interaction and implicates a role for PHF6 in chromatin structure modulation and gene regulation.

PubMed: 25601084
DOI: 10.1074/jbc.M114.610196

実験手法

X-RAY DIFFRACTION (1.85 Å)