Multiple integrase functions are required to form the native structure of the human immunodeficiency virus type I intasome. Molecular and genetic determinants of rous sarcoma virus integrase for concerted DNA integration. Structure-based mutational analysis of the C-terminal DNA-binding domain of human immunodeficiency virus type 1 integrase: critical residues for protein oligomerization and DNA binding. Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. Human immunodeficiency virus type 1 integrase: arrangement of protein domains in active cDNA complexes. Structural organization of avian retrovirus integrase in assembled intasomes mediating full-site integration. Crystal structure of an active two-domain derivative of Rous sarcoma virus integrase. Assembly of prototype foamy virus strand transfer complexes on product DNA bypassing catalysis of integration.
A possible role for the asymmetric C-terminal domain dimer of Rous sarcoma virus integrase in viral DNA binding. Solution conformations of prototype foamy virus integrase and its stable synaptic complex with U5 viral DNA. Structural basis for retroviral integration into nucleosomes. The mechanism of retroviral integration from X-ray structures of its key intermediates. Retroviral intasome assembly and inhibition of DNA strand transfer. Our work highlights the diversity of retrovirus intasome assembly and provides insights into the mechanisms of integration by HIV-1 and related retroviruses.Ĭraigie, R. The individual domains of the eight integrase molecules play varying roles to hold the complex together, making an extensive network of protein–DNA and protein–protein contacts that show both conserved and distinct features compared with those observed for prototype foamy virus integrase. The structure shows an octameric assembly of integrase, in which a pair of integrase dimers engage viral DNA ends for catalysis while another pair of non-catalytic integrase dimers bridge between the two viral DNA molecules and help capture target DNA. Here we report a crystal structure of the three-domain integrase from Rous sarcoma virus in complex with viral and target DNAs. Although structures of the tetrameric integrase–DNA complexes have been reported for integrase from prototype foamy virus featuring an additional DNA-binding domain and longer interdomain linkers 2, 3, 4, 5, the architecture of a canonical three-domain integrase bound to DNA remained elusive.
Integrase from HIV-1 and closely related retroviruses share the three-domain organization, consisting of a catalytic core domain flanked by amino- and carboxy-terminal domains essential for the concerted integration reaction. Retrovirus integrase catalyses insertions of both ends of the linear viral DNA into a host chromosome 1. Integration of the reverse-transcribed viral DNA into the host genome is an essential step in the life cycle of retroviruses.