Structural reorganization of the chromatin remodeling enzyme Chd1 upon engagement with nucleosomes

Ramasubramanian Sundaramoorthy; Amanda L. Hughes; Vijender Singh; Nicola Wiechens; Daniel P. Ryan; Hassane El-Mkami; Maxim  Petoukhov; Dmitri I. Svergun; Barbara Treutlein; Salina Quack; Monika Fischer; Jens Michaelis; Bettina Bottcher; David G. Norman; Tom Owen-Hughes

doi:10.7554/eLife.22510

Structural reorganization of the chromatin remodeling enzyme Chd1 upon engagement with nucleosomes

Ramasubramanian Sundaramoorthy, Amanda L. Hughes, Vijender Singh, Nicola Wiechens, Daniel P. Ryan, Hassane El-Mkami, Maxim Petoukhov, Dmitri I. Svergun, Barbara Treutlein, Salina Quack, Monika Fischer, Jens Michaelis, Bettina Bottcher, David G. Norman, Tom Owen-Hughes (Lead / Corresponding author)

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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.

Original language	English
Article number	e22510
Number of pages	28
Journal	eLife
Volume	6
Early online date	23 Mar 2017
DOIs	https://doi.org/10.7554/eLife.22510
Publication status	Published - 13 Apr 2017

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10.7554/eLife.22510Licence: CC BY

Final Published Version
Copyright 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.
Final published version, 5.66 MBLicence: CC BY

Strategic Award: Wellcome Trust Technology Platform
Blow, J., Lamond, A. & Owen-Hughes, T.
Wellcome Trust
1/01/13 → 30/09/18
Project: Research
State of the Art Pulse EPR Instrumentation for Long Range Distance Measurements in Biomacromolecules (Multi-User Equipment Grant) (Joint with University of St Andrews)
Hunter, B., Keeble, D., Lilley, D., Norman, D. & Owen-Hughes, T.
Wellcome Trust
24/09/12 → 23/09/17
Project: Research
State-of-the-Art Facilities for Structural Biology at the University of Dundee
Hunter, B., Lilley, D., Owen-Hughes, T., Wyatt, P. & van Aalten, D.
Wellcome Trust
1/03/12 → 28/02/17
Project: Research

Owen-Hughes, Tom
- Molecular Cell and Developmental Biology - Professor of Chromatin Structure and Dynamics
Person: Academic

Cite this

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., Bottcher, B., Norman, D. G., & Owen-Hughes, T. (2017). Structural reorganization of the chromatin remodeling enzyme Chd1 upon engagement with nucleosomes. eLife, 6, Article e22510. https://doi.org/10.7554/eLife.22510

@article{966502f23c9941a8b848aadd0fdf1250,

title = "Structural reorganization of the chromatin remodeling enzyme Chd1 upon engagement with nucleosomes",

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.",

author = "Ramasubramanian Sundaramoorthy and Hughes, {Amanda L.} and Vijender Singh and Nicola Wiechens and Ryan, {Daniel P.} and Hassane El-Mkami and Maxim Petoukhov and Svergun, {Dmitri I.} and Barbara Treutlein and Salina Quack and Monika Fischer and Jens Michaelis and Bettina Bottcher and Norman, {David G.} and Tom Owen-Hughes",

note = "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). Finally we would like to thank reviewers for useful suggestions in revising the manuscript.",

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month = apr,

day = "13",

doi = "10.7554/eLife.22510",

language = "English",

volume = "6",

journal = "eLife",

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T1 - Structural reorganization of the chromatin remodeling enzyme Chd1 upon engagement with nucleosomes

AU - Sundaramoorthy, Ramasubramanian

AU - Hughes, Amanda L.

AU - Singh, Vijender

AU - Wiechens, Nicola

AU - Ryan, Daniel P.

AU - El-Mkami, Hassane

AU - Petoukhov, Maxim

AU - Svergun, Dmitri I.

AU - Treutlein, Barbara

AU - Quack, Salina

AU - Fischer, Monika

AU - Michaelis, Jens

AU - Bottcher, Bettina

AU - Norman, David G.

AU - Owen-Hughes, Tom

N1 - 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). Finally we would like to thank reviewers for useful suggestions in revising the manuscript.

PY - 2017/4/13

Y1 - 2017/4/13

N2 - 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.

AB - 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.

U2 - 10.7554/eLife.22510

DO - 10.7554/eLife.22510

M3 - Article

C2 - 28332978

SN - 2050-084X

VL - 6

JO - eLife

JF - eLife

M1 - e22510

ER -

Structural reorganization of the chromatin remodeling enzyme Chd1 upon engagement with nucleosomes

Abstract

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Projects

Strategic Award: Wellcome Trust Technology Platform

State of the Art Pulse EPR Instrumentation for Long Range Distance Measurements in Biomacromolecules (Multi-User Equipment Grant) (Joint with University of St Andrews)

State-of-the-Art Facilities for Structural Biology at the University of Dundee

Profiles

Owen-Hughes, Tom

Cite this