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Structural basis for retroviral integration into nucleosomes
Retroviral integration is catalyzed by a tetramer of integrase (IN) assembled on viral DNA ends in a stable complex, known as the intasome(1,2). How the intasome interfaces with chromosomal DNA, which exists in the form of nucleosomal arrays, is currently unknown. Here we show that the prototype foa...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530500/ https://www.ncbi.nlm.nih.gov/pubmed/26061770 http://dx.doi.org/10.1038/nature14495 |
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author | Maskell, Daniel P. Renault, Ludovic Serrao, Erik Lesbats, Paul Matadeen, Rishi Hare, Stephen Lindemann, Dirk Engelman, Alan N. Costa, Alessandro Cherepanov, Peter |
author_facet | Maskell, Daniel P. Renault, Ludovic Serrao, Erik Lesbats, Paul Matadeen, Rishi Hare, Stephen Lindemann, Dirk Engelman, Alan N. Costa, Alessandro Cherepanov, Peter |
author_sort | Maskell, Daniel P. |
collection | PubMed |
description | Retroviral integration is catalyzed by a tetramer of integrase (IN) assembled on viral DNA ends in a stable complex, known as the intasome(1,2). How the intasome interfaces with chromosomal DNA, which exists in the form of nucleosomal arrays, is currently unknown. Here we show that the prototype foamy virus (PFV) intasome is proficient at stable capture of nucleosomes as targets for integration. Single-particle cryo-electron microscopy (EM) reveals a multivalent intasome-nucleosome interface involving both gyres of nucleosomal DNA and one H2A-H2B heterodimer. While the histone octamer remains intact, the DNA is lifted from the surface of the H2A-H2B heterodimer to allow integration at strongly preferred superhelix location (SHL) ±3.5 positions. Amino acid substitutions disrupting these contacts impinge on the ability of the intasome to engage nucleosomes in vitro and redistribute viral integration sites on the genomic scale. Our findings elucidate the molecular basis for nucleosome capture by the viral DNA recombination machinery and the underlying nucleosome plasticity that allows integration. |
format | Online Article Text |
id | pubmed-4530500 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-45305002016-01-16 Structural basis for retroviral integration into nucleosomes Maskell, Daniel P. Renault, Ludovic Serrao, Erik Lesbats, Paul Matadeen, Rishi Hare, Stephen Lindemann, Dirk Engelman, Alan N. Costa, Alessandro Cherepanov, Peter Nature Article Retroviral integration is catalyzed by a tetramer of integrase (IN) assembled on viral DNA ends in a stable complex, known as the intasome(1,2). How the intasome interfaces with chromosomal DNA, which exists in the form of nucleosomal arrays, is currently unknown. Here we show that the prototype foamy virus (PFV) intasome is proficient at stable capture of nucleosomes as targets for integration. Single-particle cryo-electron microscopy (EM) reveals a multivalent intasome-nucleosome interface involving both gyres of nucleosomal DNA and one H2A-H2B heterodimer. While the histone octamer remains intact, the DNA is lifted from the surface of the H2A-H2B heterodimer to allow integration at strongly preferred superhelix location (SHL) ±3.5 positions. Amino acid substitutions disrupting these contacts impinge on the ability of the intasome to engage nucleosomes in vitro and redistribute viral integration sites on the genomic scale. Our findings elucidate the molecular basis for nucleosome capture by the viral DNA recombination machinery and the underlying nucleosome plasticity that allows integration. 2015-06-10 2015-07-16 /pmc/articles/PMC4530500/ /pubmed/26061770 http://dx.doi.org/10.1038/nature14495 Text en Reprints and permissions information is available at www.nature.com/reprints (http://www.nature.com/reprints) . |
spellingShingle | Article Maskell, Daniel P. Renault, Ludovic Serrao, Erik Lesbats, Paul Matadeen, Rishi Hare, Stephen Lindemann, Dirk Engelman, Alan N. Costa, Alessandro Cherepanov, Peter Structural basis for retroviral integration into nucleosomes |
title | Structural basis for retroviral integration into nucleosomes |
title_full | Structural basis for retroviral integration into nucleosomes |
title_fullStr | Structural basis for retroviral integration into nucleosomes |
title_full_unstemmed | Structural basis for retroviral integration into nucleosomes |
title_short | Structural basis for retroviral integration into nucleosomes |
title_sort | structural basis for retroviral integration into nucleosomes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530500/ https://www.ncbi.nlm.nih.gov/pubmed/26061770 http://dx.doi.org/10.1038/nature14495 |
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