title: Concerted action of the PHD, chromo and motor domains regulates the human chromatin remodelling ATPase CHD4.
abstract: CHD4, the core subunit of the Nucleosome Remodelling and Deacetylase (NuRD) complex, is a chromatin remodelling ATPase that, in addition to a helicase domain, harbors tandem plant homeo finger and chromo domains. By using a panel of domain constructs we dissect their roles and demonstrate that DNA binding, histone binding and ATPase activities are allosterically regulated. Molecular shape reconstruction from small-angle X-ray scattering reveals extensive domain-domain interactions, which provide a structural explanation for the regulation of CHD4 activities by intramolecular domain communication. Our results demonstrate functional interdependency between domains within a chromatin remodeller.
authors: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, Oxford University, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.
authors: Rosa
authors: R
authors: Morra
authors: Benjamin M
authors: BM
authors: Lee
authors: Heather
authors: H
authors: Shaw
authors: Roman
authors: R
authors: Tuma
authors: Erika J
authors: EJ
authors: Mancini
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry*; D000495:Allosteric Site; D001324:Autoantigens / Q000737:chemistry*; D002843:Chromatin / Q000737:chemistry*; D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000737:chemistry; D004265:DNA Helicases / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism; D005786:Gene Expression Regulation; D006657:Histones / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000737:chemistry*; D009707:Nucleosomes / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012542:Scattering, Radiation; D020349:Surface Plasmon Resonance
chemical_list: D001324:Autoantigens; C115323:CHD4 protein, human; D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D004247:DNA; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D000251:Adenosine Triphosphatases; D004265:DNA Helicases