Abstract

Retroviral integrase can efficiently utilise nucleosomes for insertion of the reverse-transcribed viral DNA. In face of the structural constraints imposed by the nucleosomal structure, integrase gains access to the scissile phosphodiester bonds by lifting DNA off the histone octamer at the site of integration. To clarify the mechanism of DNA looping by integrase, we determined a 3.9 Å resolution structure of the prototype foamy virus intasome engaged with a nucleosome core particle. The structural data along with complementary single-molecule Förster resonance energy transfer measurements reveal twisting and sliding of the nucleosomal DNA arm proximal to the integration site. Sliding the nucleosomal DNA by approximately two base pairs along the histone octamer accommodates the necessary DNA lifting from the histone H2A-H2B subunits to allow engagement with the intasome. Thus, retroviral integration into nucleosomes involves the looping-and-sliding mechanism for nucleosomal DNA repositioning, bearing unexpected similarities to chromatin remodelers.

Details

Title
Retroviral integration into nucleosomes through DNA looping and sliding along the histone octamer
Author
Wilson, Marcus D 1   VIAFID ORCID Logo  ; Renault, Ludovic 2 ; Maskell, Daniel P 3   VIAFID ORCID Logo  ; Ghoneim, Mohamed 4 ; Pye, Valerie E 5   VIAFID ORCID Logo  ; Nans, Andrea 6 ; Rueda, David S 4   VIAFID ORCID Logo  ; Cherepanov, Peter 7 ; Costa, Alessandro 8   VIAFID ORCID Logo 

1  Macromolecular Machines Laboratory, The Francis Crick Institute, London, UK; Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, UK 
2  Macromolecular Machines Laboratory, The Francis Crick Institute, London, UK; NeCEN, University of Leiden, Leiden, Netherlands 
3  Chromatin structure and mobile DNA Laboratory, The Francis Crick Institute, London, UK; Faculty of Biological Sciences, Leeds, UK 
4  Single Molecule Imaging Group, MRC London Institute for Medical Science, London, UK; Molecular Virology, Department of Medicine, Imperial College London, London, UK 
5  Chromatin structure and mobile DNA Laboratory, The Francis Crick Institute, London, UK 
6  Structural Biology Science Technology Platform, The Francis Crick Institute, London, UK 
7  Chromatin structure and mobile DNA Laboratory, The Francis Crick Institute, London, UK; Department of Medicine, Imperial College London, St-Maryʹs Campus, Norfolk Place, London, UK 
8  Macromolecular Machines Laboratory, The Francis Crick Institute, London, UK 
Pages
1-10
Publication year
2019
Publication date
Sep 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-12007-w
ProQuest document ID
2290064136
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.