PDBsum entry 4r7a

Gene regulation

PDB id: 4r7a

Contents

Protein chain

366 a.a.

Ligands

SER-ARG-LYS-GLY-ARG-PRO-ARG-LYS-THR

GOL

Waters ×267

PDB id:

4r7a

Name:

Gene regulation

Title:

Crystal structure of rbbp4 bound to phf6 peptide

Structure:

Phd finger protein 6. Chain: a. Fragment: unp residues 157-171. Synonym: phd-like zinc finger protein. Engineered: yes. Histone-binding protein rbbp4. Chain: b. Synonym: chromatin assembly factor 1 subunit c, caf-1 subunit c, chromatin assembly factor i p48 subunit, caf-i 48 kda subunit, caf-i

Source:

Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Other_details: this sequence occurs naturally in humans. Gene: rbbp4, rbap48. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Resolution:

1.85Å R-factor: 0.178 R-free: 0.207

Authors:

Z.Liu,F.Li,B.Zhang,S.Li,J.Wu,Y.Shi

Key ref:

Z.Liu et al. (2015). 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. PubMed id: 25601084 DOI: 10.1074/jbc.M114.610196

Date:

27-Aug-14 Release date: 14-Jan-15

Protein chain

Q09028  (RBBP4_HUMAN) -  Histone-binding protein RBBP4 from Homo sapiens

Seq: 425 a.a.

Struc: 366 a.a.

DOI no: 10.1074/jbc.M114.610196

J Biol Chem 290:6630-6638 (2015)

PubMed id: 25601084

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.

Z.Liu, F.Li, B.Zhang, S.Li, J.Wu, Y.Shi.

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.