Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome

Ramasubramanian Sundaramoorthy, Amanda Hughes, Hassane El-Mkami, David Norman, Thomas Owen-Hughes (Lead / Corresponding author)

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Abstract

ATP-dependent chromatin remodelling proteins represent a diverse family of proteins that share ATPase domains that are adapted to regulate protein-DNA interactions. Here we present structures of the Saccharomyces cerevisiae Chd1 protein engaged with nucleosomes in the presence of the transition state mimic ADP-beryllium fluoride. The path of DNA strands through the ATPase domains indicates the presence of contacts conserved with single strand translocases and additional contacts with both strands that are unique to Snf2 related proteins. The structure provides connectivity between rearrangement of ATPase lobes to a closed, nucleotide bound state and the sensing of linker DNA. Two turns of linker DNA are prised off the surface of the histone octamer as a result of Chd1 binding, and both the histone H3 tail and ubiquitin conjugated to lysine 120 are re-orientated towards the unravelled DNA. This indicates how changes to nucleosome structure can alter the way in which histone epitopes are presented.
Original languageEnglish
Article numbere35720
Pages (from-to)1-28
Number of pages28
JournaleLife
Volume2018
Issue number7
Early online date6 Aug 2018
DOIs
Publication statusPublished - 6 Aug 2018

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Chromatin Assembly and Disassembly
Nucleosomes
Chromatin
Histones
DNA
Adenosine Triphosphatases
Enzymes
Proteins
Saccharomyces cerevisiae Proteins
Ubiquitin
Yeast
Adenosine Diphosphate
Lysine
Epitopes
Nucleotides
Adenosine Triphosphate

Cite this

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abstract = "ATP-dependent chromatin remodelling proteins represent a diverse family of proteins that share ATPase domains that are adapted to regulate protein-DNA interactions. Here we present structures of the Saccharomyces cerevisiae Chd1 protein engaged with nucleosomes in the presence of the transition state mimic ADP-beryllium fluoride. The path of DNA strands through the ATPase domains indicates the presence of contacts conserved with single strand translocases and additional contacts with both strands that are unique to Snf2 related proteins. The structure provides connectivity between rearrangement of ATPase lobes to a closed, nucleotide bound state and the sensing of linker DNA. Two turns of linker DNA are prised off the surface of the histone octamer as a result of Chd1 binding, and both the histone H3 tail and ubiquitin conjugated to lysine 120 are re-orientated towards the unravelled DNA. This indicates how changes to nucleosome structure can alter the way in which histone epitopes are presented.",
author = "Ramasubramanian Sundaramoorthy and Amanda Hughes and Hassane El-Mkami and David Norman and Thomas 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).",
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AU - Hughes, Amanda

AU - El-Mkami, Hassane

AU - Norman, David

AU - Owen-Hughes, Thomas

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).

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AB - ATP-dependent chromatin remodelling proteins represent a diverse family of proteins that share ATPase domains that are adapted to regulate protein-DNA interactions. Here we present structures of the Saccharomyces cerevisiae Chd1 protein engaged with nucleosomes in the presence of the transition state mimic ADP-beryllium fluoride. The path of DNA strands through the ATPase domains indicates the presence of contacts conserved with single strand translocases and additional contacts with both strands that are unique to Snf2 related proteins. The structure provides connectivity between rearrangement of ATPase lobes to a closed, nucleotide bound state and the sensing of linker DNA. Two turns of linker DNA are prised off the surface of the histone octamer as a result of Chd1 binding, and both the histone H3 tail and ubiquitin conjugated to lysine 120 are re-orientated towards the unravelled DNA. This indicates how changes to nucleosome structure can alter the way in which histone epitopes are presented.

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