| Title: |
Human H4 tail stimulates HIV-1 integration through binding to the carboxy-terminal domain of integrase |
| Authors: |
Mauro, Eric; Lesbats, Paul; Lapaillerie, Delphine; Chaignepain, Stéphane; Maillot, Benoit; Oladosu, Oyindamola; Robert, Xavier; Fiorini, Francesca; Kieffer, Bruno; Bouaziz, Serge; Gouet, Patrice; Ruff, Marc; Parissi, Vincent |
| Contributors: |
Microbiologie Fondamentale et Pathogénicité (MFP); Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS); Chimie et Biologie des Membranes et des Nanoobjets (CBMN); Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS); Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC); Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Microbiologie moléculaire et biochimie structurale - Molecular Microbiology and Structural Biochemistry (MMSB); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS); Cibles Thérapeutiques et conception de médicaments (CiTCoM - UMR 8038); Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS); ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010) |
| Source: |
ISSN: 0305-1048. |
| Publisher Information: |
CCSD; Oxford University Press |
| Publication Year: |
2019 |
| Subject Terms: |
Bobinage; Matériaux Composites; Réservoir; [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry; Molecular Biology/Structural Biology [q-bio.BM]; [CHIM.MATE]Chemical Sciences/Material chemistry; [PHYS.MECA.MEMA]Physics [physics]/Mechanics [physics]/Mechanics of materials [physics.class-ph]; [SPI.MECA.MEFL]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph] |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/30767014; PUBMED: 30767014 |
| DOI: |
10.1093/nar/gkz091 |
| Availability: |
https://hal.science/hal-02122315; https://hal.science/hal-02122315v1/document; https://hal.science/hal-02122315v1/file/gkz091.pdf; https://doi.org/10.1093/nar/gkz091 |
| Rights: |
http://creativecommons.org/licenses/by-nc-nd/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.3D82E3F7 |
| Database: |
BASE |