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Human H4 tail stimulates HIV-1 integration through binding to the carboxy-terminal domain of integrase.
Langue
EN
Article de revue
Ce document a été publié dans
Nucleic Acids Research. 2019-04-23, vol. 47, n° 7, p. 3607-3618
Résumé en anglais
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 ...Lire la suite >
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.< Réduire
Mots clés en anglais
Catalysis
Chromatin
Genome
Viral
HIV Integrase
HIV-1
Histones
Host-Pathogen Interactions
Humans
Nucleosomes
Spumavirus
Virus Integration
Unités de recherche