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PMID: 16482214 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

Retroviral DNA integration: reaction pathway and critical intermediates.

The EMBO journal ·Vol. 25 ·No. 6 ·2006-03-22 ·Pages 1295-304

Li M, Mizuuchi M, Burke TR, Craigie R

Abstract

The key DNA cutting and joining steps of retroviral DNA integration are carried out by the viral integrase protein. Structures of the individual domains of integrase have been determined, but their organization in the active complex with viral DNA is unknown. We show that HIV-1 integrase forms stable synaptic complexes in which a tetramer of integrase is stably associated with a pair of viral DNA ends. The viral DNA is processed within these complexes, which go on to capture the target DNA and integrate the viral DNA ends. The joining of the two viral DNA ends to target DNA occurs sequentially, with a stable intermediate complex in which only one DNA end is joined. The integration product also remains stably associated with integrase and likely requires disassembly before completion of the integration process by cellular enzymes. The results define the series of stable nucleoprotein complexes that mediate retroviral DNA integration.

MeSH Terms
Blotting, Western Cross-Linking Reagents DNA Footprinting DNA, Viral/chemistry,metabolism HIV Integrase/metabolism HIV-1/genetics,physiology Humans Recombinant Proteins/metabolism Retroviridae/physiology Virus Integration
Chemicals
Cross-Linking Reagents DNA, Viral Recombinant Proteins HIV Integrase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Li Min
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Mizuuchi Michiyo
Burke Terrence R
Craigie Robert
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7601005
Published
2006-03-22
Epub
2006-00-16
Pages
1295-304
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1422164
Subset
IM
Grants
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1038/sj.emboj.7601005 PMC Full Text View journal details
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