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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-...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
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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. |
format | Online Article Text |
id | pubmed-6611695 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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