title: The chromodomains of the Chd1 chromatin remodeler regulate DNA access to the ATPase motor.
abstract: Chromatin remodelers are ATP-driven machines that assemble, slide, and remove nucleosomes from DNA, but how the ATPase motors of remodelers are regulated is poorly understood. Here we show that the double chromodomain unit of the Chd1 remodeler blocks DNA binding and activation of the ATPase motor in the absence of nucleosome substrates. The Chd1 crystal structure reveals that an acidic helix joining the chromodomains can pack against a DNA-binding surface of the ATPase motor. Disruption of the chromodomain-ATPase interface prevents discrimination between nucleosomes and naked DNA and reduces the reliance on the histone H4 tail for nucleosome sliding. We propose that the chromodomains allow Chd1 to distinguish between nucleosomes and naked DNA by physically gating access to the ATPase motor, and we hypothesize that related ATPase motors may employ a similar strategy to discriminate among DNA-containing substrates.
authors.affiliation: TC Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218-2685, USA.
authors.forename: Glenn
authors.initials: G
authors.lastname: Hauk
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: McKnight
authors.forename: Ilana M
authors.initials: IM
authors.lastname: Nodelman
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Bowman
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000502:physiology; D018360:Crystallography, X-Ray; D004271:DNA, Fungal / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C489847:CHD1 protein, S cerevisiae; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D006657:Histones; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases