Publication Date:
2010-11-12
Description:
To establish productive infection, a retrovirus must insert a DNA replica of its genome into host cell chromosomal DNA. This process is operated by the intasome, a nucleoprotein complex composed of an integrase tetramer (IN) assembled on the viral DNA ends. The intasome engages chromosomal DNA within a target capture complex to carry out strand transfer, irreversibly joining the viral and cellular DNA molecules. Although several intasome/transpososome structures from the DDE(D) recombinase superfamily have been reported, the mechanics of target DNA capture and strand transfer by these enzymes remained unclear. Here we report crystal structures of the intasome from prototype foamy virus in complex with target DNA, elucidating the pre-integration target DNA capture and post-catalytic strand transfer intermediates of the retroviral integration process. The cleft between IN dimers within the intasome accommodates chromosomal DNA in a severely bent conformation, allowing widely spaced IN active sites to access the scissile phosphodiester bonds. Our results resolve the structural basis for retroviral DNA integration and provide a framework for the design of INs with altered target sequences.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999894/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999894/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maertens, Goedele N -- Hare, Stephen -- Cherepanov, Peter -- G0900116/Medical Research Council/United Kingdom -- G0900116(90753)/Medical Research Council/United Kingdom -- G1000917/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2010 Nov 11;468(7321):326-9. doi: 10.1038/nature09517.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Infectious Diseases, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21068843" target="_blank"〉PubMed〈/a〉
Keywords:
Base Sequence
;
Catalytic Domain
;
Crystallography, X-Ray
;
DNA/chemistry/genetics/metabolism
;
Integrases/genetics/metabolism
;
Models, Molecular
;
Molecular Conformation
;
Spumavirus/*chemistry/enzymology/*physiology
;
*Virus Integration
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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