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Cryo-EM structures of remodeler-nucleosome intermediates suggest allosteric control through the nucleosome

The SNF2h remodeler slides nucleosomes most efficiently as a dimer, yet how the two protomers avoid a tug-of-war is unclear. Furthermore, SNF2h couples histone octamer deformation to nucleosome sliding, but the underlying structural basis remains unknown. Here we present cryo-EM structures of SNF2h-...

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Autores principales: Armache, Jean Paul, Gamarra, Nathan, Johnson, Stephanie L, Leonard, John D, Wu, Shenping, Narlikar, Geeta J, Cheng, Yifan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611695/
https://www.ncbi.nlm.nih.gov/pubmed/31210637
http://dx.doi.org/10.7554/eLife.46057
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author Armache, Jean Paul
Gamarra, Nathan
Johnson, Stephanie L
Leonard, John D
Wu, Shenping
Narlikar, Geeta J
Cheng, Yifan
author_facet Armache, Jean Paul
Gamarra, Nathan
Johnson, Stephanie L
Leonard, John D
Wu, Shenping
Narlikar, Geeta J
Cheng, Yifan
author_sort Armache, Jean Paul
collection PubMed
description The SNF2h remodeler slides nucleosomes most efficiently as a dimer, yet how the two protomers avoid a tug-of-war is unclear. Furthermore, SNF2h couples histone octamer deformation to nucleosome sliding, but the underlying structural basis remains unknown. Here we present cryo-EM structures of SNF2h-nucleosome complexes with ADP-BeF(x) that capture two potential reaction intermediates. In one structure, histone residues near the dyad and in the H2A-H2B acidic patch, distal to the active SNF2h protomer, appear disordered. The disordered acidic patch is expected to inhibit the second SNF2h protomer, while disorder near the dyad is expected to promote DNA translocation. The other structure doesn’t show octamer deformation, but surprisingly shows a 2 bp translocation. FRET studies indicate that ADP-BeF(x) predisposes SNF2h-nucleosome complexes for an elemental translocation step. We propose a model for allosteric control through the nucleosome, where one SNF2h protomer promotes asymmetric octamer deformation to inhibit the second protomer, while stimulating directional DNA translocation.
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spelling pubmed-66116952019-07-08 Cryo-EM structures of remodeler-nucleosome intermediates suggest allosteric control through the nucleosome Armache, Jean Paul Gamarra, Nathan Johnson, Stephanie L Leonard, John D Wu, Shenping Narlikar, Geeta J Cheng, Yifan eLife Chromosomes and Gene Expression The SNF2h remodeler slides nucleosomes most efficiently as a dimer, yet how the two protomers avoid a tug-of-war is unclear. Furthermore, SNF2h couples histone octamer deformation to nucleosome sliding, but the underlying structural basis remains unknown. Here we present cryo-EM structures of SNF2h-nucleosome complexes with ADP-BeF(x) that capture two potential reaction intermediates. In one structure, histone residues near the dyad and in the H2A-H2B acidic patch, distal to the active SNF2h protomer, appear disordered. The disordered acidic patch is expected to inhibit the second SNF2h protomer, while disorder near the dyad is expected to promote DNA translocation. The other structure doesn’t show octamer deformation, but surprisingly shows a 2 bp translocation. FRET studies indicate that ADP-BeF(x) predisposes SNF2h-nucleosome complexes for an elemental translocation step. We propose a model for allosteric control through the nucleosome, where one SNF2h protomer promotes asymmetric octamer deformation to inhibit the second protomer, while stimulating directional DNA translocation. eLife Sciences Publications, Ltd 2019-06-18 /pmc/articles/PMC6611695/ /pubmed/31210637 http://dx.doi.org/10.7554/eLife.46057 Text en © 2019, Armache et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Chromosomes and Gene Expression
Armache, Jean Paul
Gamarra, Nathan
Johnson, Stephanie L
Leonard, John D
Wu, Shenping
Narlikar, Geeta J
Cheng, Yifan
Cryo-EM structures of remodeler-nucleosome intermediates suggest allosteric control through the nucleosome
title Cryo-EM structures of remodeler-nucleosome intermediates suggest allosteric control through the nucleosome
title_full Cryo-EM structures of remodeler-nucleosome intermediates suggest allosteric control through the nucleosome
title_fullStr Cryo-EM structures of remodeler-nucleosome intermediates suggest allosteric control through the nucleosome
title_full_unstemmed Cryo-EM structures of remodeler-nucleosome intermediates suggest allosteric control through the nucleosome
title_short Cryo-EM structures of remodeler-nucleosome intermediates suggest allosteric control through the nucleosome
title_sort cryo-em structures of remodeler-nucleosome intermediates suggest allosteric control through the nucleosome
topic Chromosomes and Gene Expression
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611695/
https://www.ncbi.nlm.nih.gov/pubmed/31210637
http://dx.doi.org/10.7554/eLife.46057
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