title: Insight into the architecture of the NuRD complex: structure of the RbAp48-MTA1 subcomplex.
abstract: The nucleosome remodeling and deacetylase (NuRD) complex is a widely conserved transcriptional co-regulator that harbors both nucleosome remodeling and histone deacetylase activities. It plays a critical role in the early stages of ES cell differentiation and the reprogramming of somatic to induced pluripotent stem cells. Abnormalities in several NuRD proteins are associated with cancer and aging. We have investigated the architecture of NuRD by determining the structure of a subcomplex comprising RbAp48 and MTA1. Surprisingly, RbAp48 recognizes MTA1 using the same site that it uses to bind histone H4, showing that assembly into NuRD modulates RbAp46/48 interactions with histones. Taken together with other results, our data show that the MTA proteins act as scaffolds for NuRD complex assembly. We further show that the RbAp48-MTA1 interaction is essential for the in vivo integration of RbAp46/48 into the NuRD complex.
authors.affiliation: From the School of Molecular Bioscience, University of Sydney, New South Wales 2006, Australia.
authors.forename: Saad S M
authors.initials: SS
authors.lastname: Alqarni
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
authors.forename: Andal
authors.initials: A
authors.lastname: Murthy
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Genetics, University of Cambridge, CB2 3EH, United Kingdom.
authors.forename: Marcin R
authors.initials: MR
authors.lastname: Przewloka
authors.affiliation: From the School of Molecular Bioscience, University of Sydney, New South Wales 2006, Australia.
authors.forename: Ana P G
authors.initials: AP
authors.lastname: Silva
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
authors.forename: Aleksandra A
authors.initials: AA
authors.lastname: Watson
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
authors.forename: Sara
authors.initials: S
authors.lastname: Lejon
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
authors.forename: Xue Y
authors.initials: XY
authors.lastname: Pei
authors.affiliation: Department of Molecular Cancer Research, UMC Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands, and.
authors.forename: Arne H
authors.initials: AH
authors.lastname: Smits
authors.affiliation: Department of Molecular Cancer Research, UMC Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands, and.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Kloet
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Wang
authors.affiliation: From the School of Molecular Bioscience, University of Sydney, New South Wales 2006, Australia.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Shepherd
authors.affiliation: From the School of Molecular Bioscience, University of Sydney, New South Wales 2006, Australia.
authors.forename: Philippa H
authors.initials: PH
authors.lastname: Stokes
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Blobel
authors.affiliation: Department of Molecular Cancer Research, UMC Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands, and.
authors.forename: Michiel
authors.initials: M
authors.lastname: Vermeulen
authors.affiliation: Department of Genetics, University of Cambridge, CB2 3EH, United Kingdom.
authors.forename: David M
authors.initials: DM
authors.lastname: Glover
authors.affiliation: From the School of Molecular Bioscience, University of Sydney, New South Wales 2006, Australia, joel.mackay@sydney.edu.au.
authors.forename: Joel P
authors.initials: JP
authors.lastname: Mackay
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom, e.d.laue@bioc.cam.ac.uk.
authors.forename: Ernest D
authors.initials: ED
authors.lastname: Laue
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D042002:Chromatin Assembly and Disassembly; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006655:Histone Deacetylases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D056505:Retinoblastoma-Binding Protein 4 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D056524:Retinoblastoma-Binding Protein 7 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D006657:Histones; C089320:MTA1 protein, human; D009687:Nuclear Proteins; D009707:Nucleosomes; C082637:RBBP4 protein, human; C490746:RBBP7 protein, human; D012097:Repressor Proteins; D056505:Retinoblastoma-Binding Protein 4; D056524:Retinoblastoma-Binding Protein 7; D015534:Trans-Activators; D014157:Transcription Factors; C498432:ZFPM1 protein, human; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex
keywords: Chromatin; Chromatin Structure; Gene Regulation; MTA1; NuRD Complex; Protein Assembly; Protein Structure; RBBP4; RbAp48