Structural reorganization of the chromatin remodeling enzyme Chd1 upon engagement with nucleosomes
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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.
Sundaramoorthy , R , Hughes , A L , Singh , V , Wiechens , N , Ryan , D P , El-Mkami , H , Petoukhov , M , Svergun , D I , Treutlein , B , Quack , S , Fischer , M , Michaelis , J , Böttcher , B , Norman , D G & Owen-Hughes , T 2017 , ' Structural reorganization of the chromatin remodeling enzyme Chd1 upon engagement with nucleosomes ' eLife , vol 6 , e22510 . DOI: 10.7554/eLife.22510
© 2017, Sundaramoorthy et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
This work was funded by Wellcome Senior Fellowship 095062, Wellcome Trust grants 094090, 099149 and 097945. ALH was funded by and EMBO long-term fellowship ALTF 380–2015 co-funded by the European Commission (LTFCOFUND2013, GA-2013–609409).
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