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Human H4 tail stimulates HIV-1 integration through binding to the carboxy-terminal domain of integrase
The integration of the retroviral genome into the chromatin of the infected cell is catalysed by the integrase (IN)•viral DNA complex (intasome). This process requires functional association between the integration complex and the nucleosomes. Direct intasome/histone contacts have been reported to m...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468294/ https://www.ncbi.nlm.nih.gov/pubmed/30767014 http://dx.doi.org/10.1093/nar/gkz091 |
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author | Mauro, Eric Lesbats, Paul Lapaillerie, Delphine Chaignepain, Stephane Maillot, Benoit Oladosu, Oyindamola Robert, Xavier Fiorini, Francesca Kieffer, Bruno Bouaziz, Serge Gouet, Patrice Ruff, Marc Parissi, Vincent |
author_facet | Mauro, Eric Lesbats, Paul Lapaillerie, Delphine Chaignepain, Stephane Maillot, Benoit Oladosu, Oyindamola Robert, Xavier Fiorini, Francesca Kieffer, Bruno Bouaziz, Serge Gouet, Patrice Ruff, Marc Parissi, Vincent |
author_sort | Mauro, Eric |
collection | PubMed |
description | The integration of the retroviral genome into the chromatin of the infected cell is catalysed by the integrase (IN)•viral DNA complex (intasome). This process requires functional association between the integration complex and the nucleosomes. Direct intasome/histone contacts have been reported to modulate the interaction between the integration complex and the target DNA (tDNA). Both prototype foamy virus (PFV) and HIV-1 integrases can directly bind histone amino-terminal tails. We have further investigated this final association by studying the effect of isolated histone tails on HIV-1 integration. We show here that the binding of HIV-1 IN to a peptide derived from the H4 tail strongly stimulates integration catalysis in vitro. This stimulation was not observed with peptide tails from other variants or with alpha-retroviral (RAV) and spuma-retroviral PFV integrases. Biochemical analyses show that the peptide tail induces both an increase in the IN oligomerization state and affinity for the target DNA, which are associated with substantial structural rearrangements in the IN carboxy-terminal domain (CTD) observed by NMR. Our data indicate that the H4 peptide tail promotes the formation of active strand transfer complexes (STCs) and support an activation step of the incoming intasome at the contact of the histone tail. |
format | Online Article Text |
id | pubmed-6468294 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-64682942019-04-22 Human H4 tail stimulates HIV-1 integration through binding to the carboxy-terminal domain of integrase Mauro, Eric Lesbats, Paul Lapaillerie, Delphine Chaignepain, Stephane Maillot, Benoit Oladosu, Oyindamola Robert, Xavier Fiorini, Francesca Kieffer, Bruno Bouaziz, Serge Gouet, Patrice Ruff, Marc Parissi, Vincent Nucleic Acids Res Nucleic Acid Enzymes The integration of the retroviral genome into the chromatin of the infected cell is catalysed by the integrase (IN)•viral DNA complex (intasome). This process requires functional association between the integration complex and the nucleosomes. Direct intasome/histone contacts have been reported to modulate the interaction between the integration complex and the target DNA (tDNA). Both prototype foamy virus (PFV) and HIV-1 integrases can directly bind histone amino-terminal tails. We have further investigated this final association by studying the effect of isolated histone tails on HIV-1 integration. We show here that the binding of HIV-1 IN to a peptide derived from the H4 tail strongly stimulates integration catalysis in vitro. This stimulation was not observed with peptide tails from other variants or with alpha-retroviral (RAV) and spuma-retroviral PFV integrases. Biochemical analyses show that the peptide tail induces both an increase in the IN oligomerization state and affinity for the target DNA, which are associated with substantial structural rearrangements in the IN carboxy-terminal domain (CTD) observed by NMR. Our data indicate that the H4 peptide tail promotes the formation of active strand transfer complexes (STCs) and support an activation step of the incoming intasome at the contact of the histone tail. Oxford University Press 2019-04-23 2019-02-15 /pmc/articles/PMC6468294/ /pubmed/30767014 http://dx.doi.org/10.1093/nar/gkz091 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Nucleic Acid Enzymes Mauro, Eric Lesbats, Paul Lapaillerie, Delphine Chaignepain, Stephane Maillot, Benoit Oladosu, Oyindamola Robert, Xavier Fiorini, Francesca Kieffer, Bruno Bouaziz, Serge Gouet, Patrice Ruff, Marc Parissi, Vincent Human H4 tail stimulates HIV-1 integration through binding to the carboxy-terminal domain of integrase |
title | Human H4 tail stimulates HIV-1 integration through binding to the carboxy-terminal domain of integrase |
title_full | Human H4 tail stimulates HIV-1 integration through binding to the carboxy-terminal domain of integrase |
title_fullStr | Human H4 tail stimulates HIV-1 integration through binding to the carboxy-terminal domain of integrase |
title_full_unstemmed | Human H4 tail stimulates HIV-1 integration through binding to the carboxy-terminal domain of integrase |
title_short | Human H4 tail stimulates HIV-1 integration through binding to the carboxy-terminal domain of integrase |
title_sort | human h4 tail stimulates hiv-1 integration through binding to the carboxy-terminal domain of integrase |
topic | Nucleic Acid Enzymes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468294/ https://www.ncbi.nlm.nih.gov/pubmed/30767014 http://dx.doi.org/10.1093/nar/gkz091 |
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