Abstract
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-BeFx that capture two 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 2bp translocation. FRET studies indicate that ADP-BeFx 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.
Article and author information
Author details
Funding
National Institutes of Health (GM073767)
- Geeta J Narlikar
National Science Foundation
- Nathan Gamarra
Howard Hughes Medical Institute
- Yifan Cheng
University of California, San Francisco (Program for Breakthrough Biomedical Research)
- Yifan Cheng
Leukemia and Lymphoma Society
- Stephanie L Johnson
National Institutes of Health (GM108455)
- Geeta J Narlikar
National Institutes of Health (R01GM082893)
- Yifan Cheng
National Institutes of Health (1S10OD020054)
- Yifan Cheng
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Sjors HW Scheres, MRC Laboratory of Molecular Biology, United Kingdom
Publication history
- Received: February 14, 2019
- Accepted: June 18, 2019
- Accepted Manuscript published: June 18, 2019 (version 1)
- Version of Record published: July 5, 2019 (version 2)
Copyright
© 2019, Armache 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.
Metrics
-
- 4,091
- Page views
-
- 644
- Downloads
-
- 16
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.