Crystal structure of the Rous sarcoma virus intasome

Zhiqi Yin, Ke Shi, Surajit Banerjee, Krishan K. Pandey, Sibes Bera, Duane P. Grandgenett, Hideki Aihara

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Integration of the reverse-transcribed viral DNA into the host genome is an essential step in the life cycle of retroviruses. Retrovirus integrase catalyses insertions of both ends of the linear viral DNA into a host chromosome. 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. 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, the architecture of a canonical three-domain integrase bound to DNA remained elusive. Here we report a crystal structure of the three-domain integrase from Rous sarcoma virus in complex with viral and target DNAs. 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. 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. Our work highlights the diversity of retrovirus intasome assembly and provides insights into the mechanisms of integration by HIV-1 and related retroviruses.

Original languageEnglish (US)
Pages (from-to)362-366
Number of pages5
JournalNature
Volume530
Issue number7590
DOIs
StatePublished - Feb 17 2016

Bibliographical note

Funding Information:
Acknowledgements We thank K. Kurahashi for generating many mutant IN expression plasmids, J. Kankanala and Z. Wang for synthesizing Pt-modified oligonucleotides, and J. Nix for help with X-ray data collection. X-ray data were collected at the Advanced Photon Source (APS) NE-CAT beamlines, which are supported by the National Institute of General Medical Sciences (P41 GM103403). APS is a US Department of Energy Office of Science User Facility operated by Argonne National Laboratory under contract DE-AC02-06CH11357. This research was supported by National Institutes of Health grants GM109770, AI087098 to H.A. and AI100682 to D.P.G.

Funding Information:
We thank K. Kurahashi for generating many mutant IN expression plasmids, J. Kankanala and Z. Wang for synthesizing Pt-modified oligonucleotides, and J. Nix for help with X-ray data collection. X-ray data were collected at the Advanced Photon Source (APS) NE-CAT beamlines, which are supported by the National Institute of General Medical Sciences (P41 GM103403). APS is a US Department of Energy Office of Science User Facility operated by Argonne National Laboratory under contract DE-AC02-06CH11357. This research was supported by National Institutes of Health grants GM109770, AI087098 to H.A. and AI100682 to D.P.G.

Publisher Copyright:
© 2016 Macmillan Publishers Limited.

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