Structural reorganization of the chromatin remodeling enzyme Chd1 upon engagement with nucleosomes.
The yeast Chd1 protein acts to position nucleosomes across genomes. Here, we model the structure of the Chd1 protein in solution and when bound to nucleosomes. In the apo state, the DNA-binding domain contacts the edge of the nucleosome while in the presence of the non-hydrolyzable ATP analog, ADP-beryllium fluoride, we observe additional interactions between the ATPase domain and the adjacent DNA gyre 1.5 helical turns from the dyad axis of symmetry. Binding in this conformation involves unravelling the outer turn of nucleosomal DNA and requires substantial reorientation of the DNA-binding domain with respect to the ATPase domains. The orientation of the DNA-binding domain is mediated by sequences in the N-terminus and mutations to this part of the protein have positive and negative effects on Chd1 activity. These observations indicate that the unfavorable alignment of C-terminal DNA-binding region in solution contributes to an auto-inhibited state.
Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
Ramasubramanian
R
Sundaramoorthy
Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
Amanda L
AL
Hughes
Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
Vijender
V
Singh
Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
Nicola
N
Wiechens
Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
Daniel P
0000-0001-9842-2620
DP
Ryan
School of Physics and Astronomy, University of St Andrews, St Andrews, United Kingdom.
Hassane
H
El-Mkami
Hamburg Outstation, European Molecular Biology Laboratory, Hamburg, Germany.
Maxim
M
Petoukhov
Hamburg Outstation, European Molecular Biology Laboratory, Hamburg, Germany.
Dmitri I
DI
Svergun
Institute for Biophysics, Faculty of Natural Sciences, Ulm University, Ulm, Germany.
Barbara
B
Treutlein
Institute for Biophysics, Faculty of Natural Sciences, Ulm University, Ulm, Germany.
Salina
S
Quack
Institute for Biophysics, Faculty of Natural Sciences, Ulm University, Ulm, Germany.
Monika
M
Fischer
Institute for Biophysics, Faculty of Natural Sciences, Ulm University, Ulm, Germany.
Jens
J
Michaelis
Lehrstuhl für Biochemie, Rudolf-Virchow Zentrum, Universitat Würzburg, Würzburg, Germany.
Bettina
B
Böttcher
Nucleic Acids Structure Research Group, University of Dundee, Dundee, United Kingdom.
David G
0000-0002-7658-7720
DG
Norman
Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
Tom
0000-0002-0618-8185
T
Owen-Hughes
D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009707:Nucleosomes / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*
C489847:CHD1 protein, S cerevisiae; D004268:DNA-Binding Proteins; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins
ATPase; Chd1; S. cerevisiae; biophysics; chromatin remodeling; chromosomes; genes; nucleosome; structural biology