Human H4 tail stimulates HIV-1 integration through binding to the carboxy-terminal domain of integrase.
Fiche publication
Date publication
février 2019
Journal
Nucleic acids research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr KIEFFER Bruno, Dr RUFF Marc
Tous les auteurs :
Mauro E, Lesbats P, Lapaillerie D, Chaignepain S, Maillot, Oladosu O, Robert X, Fiorini F, Kieffer B, Bouaziz S, Gouet P, Ruff M, Parissi V
Lien Pubmed
Résumé
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.
Référence
Nucleic Acids Res.. 2019 02 15;: