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.
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
Further reading
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- Structural Biology and Molecular Biophysics
In eukaryotes, RNAs transcribed by RNA Pol II are modified at the 5′ end with a 7-methylguanosine (m7G) cap, which is recognized by the nuclear cap binding complex (CBC). The CBC plays multiple important roles in mRNA metabolism, including transcription, splicing, polyadenylation, and export. It promotes mRNA export through direct interaction with a key mRNA export factor, ALYREF, which in turn links the TRanscription and EXport (TREX) complex to the 5′ end of mRNA. However, the molecular mechanism for CBC-mediated recruitment of the mRNA export machinery is not well understood. Here, we present the first structure of the CBC in complex with an mRNA export factor, ALYREF. The cryo-EM structure of CBC-ALYREF reveals that the RRM domain of ALYREF makes direct contact with both the NCBP1 and NCBP2 subunits of the CBC. Comparing CBC-ALYREF with other cellular complexes containing CBC and/or ALYREF components provides insights into the coordinated events during mRNA transcription, splicing, and export.
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- Structural Biology and Molecular Biophysics
Under physiological conditions, proteins continuously undergo structural fluctuations on different timescales. Some conformations are only sparsely populated, but still play a key role in protein function. Thus, meaningful structure–function frameworks must include structural ensembles rather than only the most populated protein conformations. To detail protein plasticity, modern structural biology combines complementary experimental and computational approaches. In this review, we survey available computational approaches that integrate sparse experimental data from electron paramagnetic resonance spectroscopy with molecular modeling techniques to derive all-atom structural models of rare protein conformations. We also propose strategies to increase the reliability and improve efficiency using deep learning approaches, thus advancing the field of integrative structural biology.
