4r7a
From Proteopedia
Crystal Structure of RBBP4 bound to PHF6 peptide
Structural highlights
Disease[PHF6_HUMAN] Borjeson-Forssman-Lehmann syndrome. The disease is caused by mutations affecting the gene represented in this entry. Function[PHF6_HUMAN] Transcriptional regulator that associates with ribosomal RNA promoters and suppresses ribosomal RNA (rRNA) transcription.[1] [RBBP4_HUMAN] Core histone-binding subunit that may target chromatin assembly factors, chromatin remodeling factors and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of several complexes which regulate chromatin metabolism. These include the chromatin assembly factor 1 (CAF-1) complex, which is required for chromatin assembly following DNA replication and DNA repair; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodeling; the PRC2/EED-EZH2 complex, which promotes repression of homeotic genes during development; and the NURF (nucleosome remodeling factor) complex.[2] Publication Abstract from PubMedThe NuRD complex is a conserved transcriptional coregulator that contains both chromatin-remodeling and histone deacetylase activities. Mutations of PHF6 are found in patients with Borjeson-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 beta-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. 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.,Liu Z, Li F, Zhang B, Li S, Wu J, Shi Y J Biol Chem. 2015 Mar 6;290(10):6630-8. doi: 10.1074/jbc.M114.610196. Epub 2015, Jan 19. PMID:25601084[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||
Categories: Li, F | Li, S | Liu, Z | Shi, Y | Wu, J | Zhang, B | Gene regulation | Nuclear | Wd40 repeat domain
