Structural reorganization of the chromatin remodeling enzyme Chd1 upon engagement with nucleosomes
- University of Dundee, United Kingdom
- The Australian National University, Australia
- University of St Andrews, United Kingdom
- European Molecular Biology Laboratory, Germany
- Max Planck Institute for Evolutionary Anthropolgy, Germany
- Ulm University, Germany
- Universitat Würzburg, Germany
Abstract
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 unfavourable alignment of C-terminal DNA binding region in solution contributes to an auto-inhibited state.
Data availability
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Chd1-nuc-engagedPublicly available at the Electron Microscopy Data Bank (accession no. EMDB-3502).
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Chd1 Nuc SeqPublicly available at the EMBL European Archive (accession no: PRJEB15701).
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Chd1-nuc apoPublicly available at the Electron Microscopy Data Bank (accession no. EMDB-3517).
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Data from: Structural reorganization of the chromatin remodeling enzyme Chd1 upon engagement with nucleosomesAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
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SAXSPublicly available at the Small Angle Scattering Biological Data Bank (accession no. SASDBU7).
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SAXSPublicly available at the Small Angle Scattering Biological Data Bank (accession no. SASDBV7).
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SAXSPublicly available at the Small Angle Scattering Biological Data Bank (accession no. SASDBW7).
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SAXSPublicly available at the Small Angle Scattering Biological Data Bank (accession no. SASDBX7).
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SAXSPublicly available at the Small Angle Scattering Biological Data Bank (accession no. SASDBY7).
Article and author information
Author details
Funding
Wellcome (95062)
- Ramasubramanian Sundaramoorthy
- Amanda L Hughes
- Vijender Singh
- Nicola Wiechens
- Tom Owen-Hughes
Wellcome (097945/B/11/Z)
- Ramasubramanian Sundaramoorthy
- Amanda L Hughes
- Vijender Singh
- Nicola Wiechens
- Tom Owen-Hughes
Wellcome (099149/Z/12/Z)
- Ramasubramanian Sundaramoorthy
- Hassane El-Mkami
- David G Norman
- Tom Owen-Hughes
Wellcome (97945)
- Ramasubramanian Sundaramoorthy
- Amanda L Hughes
- Nicola Wiechens
- Daniel P Ryan
- David G Norman
- Tom Owen-Hughes
European Molecular Biology Organization (ALTF 380-2015)
- Amanda L Hughes
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Timothy Formosa, University of Utah, United States
Version history
- Received: November 9, 2016
- Accepted: March 15, 2017
- Accepted Manuscript published: March 23, 2017 (version 1)
- Version of Record published: April 13, 2017 (version 2)
Copyright
© 2017, Sundaramoorthy et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Structural reorganization of the chromatin remodeling enzyme Chd1 upon engagement with nucleosomes
eLife 6:e22510.
https://doi.org/10.7554/eLife.22510
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