Insights into association of the NuRD complex with FOG-1 from the crystal structure of an RbAp48·FOG-1 complex.
Chromatin-modifying complexes such as the NuRD complex are recruited to particular genomic sites by gene-specific nuclear factors. Overall, however, little is known about the molecular basis for these interactions. Here, we present the 1.9 Å resolution crystal structure of the NuRD subunit RbAp48 bound to the 15 N-terminal amino acids of the GATA-1 cofactor FOG-1. The FOG-1 peptide contacts a negatively charged binding pocket on top of the RbAp48 β-propeller that is distinct from the binding surface used by RpAp48 to contact histone H4. We further show that RbAp48 interacts with the NuRD subunit MTA-1 via a surface that is distinct from its FOG-binding pocket, providing a first glimpse into the way in which NuRD assembly facilitates interactions with cofactors. Our RbAp48·FOG-1 structure provides insight into the molecular determinants of FOG-1-dependent association with the NuRD complex and into the links between transcription regulation and nucleosome remodeling.
Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
Sara
S
Lejon
Sock Yue
SY
Thong
Andal
A
Murthy
Saad
S
AlQarni
Natalia V
NV
Murzina
Gerd A
GA
Blobel
Ernest D
ED
Laue
Joel P
JP
Mackay
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002478:Cells, Cultured; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D056505:Retinoblastoma-Binding Protein 4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018411:Spodoptera; D015534:Trans-Activators; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*
D006657:Histones; D008840:Microfilament Proteins; C089320:MTA1 protein, human; D009687:Nuclear Proteins; C082637:RBBP4 protein, human; D011994:Recombinant Proteins; D012097:Repressor Proteins; D056505:Retinoblastoma-Binding Protein 4; D015534:Trans-Activators; D014157:Transcription Factors; C118067:WDR1 protein, human; C498432:ZFPM1 protein, human; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex