Retroviral intasome assembly and inhibition of DNA strand transfer

Hare, Stephen, Gupta, Saumya Shree, Valkov, Eugene, Engelman, Alan and Cherepanov, Peter (2010) Retroviral intasome assembly and inhibition of DNA strand transfer. Nature, 464 7286: 232-236. doi:10.1038/nature08784

Author Hare, Stephen
Gupta, Saumya Shree
Valkov, Eugene
Engelman, Alan
Cherepanov, Peter
Title Retroviral intasome assembly and inhibition of DNA strand transfer
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
Publication date 2010-03
Sub-type Article (original research)
DOI 10.1038/nature08784
Volume 464
Issue 7286
Start page 232
End page 236
Total pages 5
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract Integrase is an essential retroviral enzyme that binds both termini of linear viral DNA and inserts them into a host cell chromosome. The structure of full-length retroviral integrase, either separately or in complex with DNA, has been lacking. Furthermore, although clinically useful inhibitors of HIV integrase have been developed, their mechanism of action remains speculative. Here we present a crystal structure of full-length integrase from the prototype foamy virus in complex with its cognate DNA. The structure shows the organization of the retroviral intasome comprising an integrase tetramer tightly associated with a pair of viral DNA ends. All three canonical integrase structural domains are involved in extensive protein–DNA and protein–protein interactions. The binding of strand-transfer inhibitors displaces the reactive viral DNA end from the active site, disarming the viral nucleoprotein complex. Our findings define the structural basis of retroviral DNA integration, and will allow modelling of the HIV-1 intasome to aid in the development of antiretroviral drugs.
Keyword Automated Structure Solution
Sarcoma-Virus Integrase
HIV-1 Integrase
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
School of Chemistry and Molecular Biosciences
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