ArticleNucleic acids research2011
FRET analysis reveals distinct conformations of IN tetramers in the presence of viral DNA or LEDGF/p75.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- HIV-1 Integrase Inhibition Activity by Spiroketals Derived fromPharmaceuticals (Basel, Switzerland) · 2023Article
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- Implications of Fragment-Based Drug Discovery in Tuberculosis and HIV.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Multimodal Functionalities of HIV-1 Integrase.Viruses · 2022Review
- HIV-1 integrase binding to genomic RNA 5'-UTR induces local structural changes in vitro and in virio.Retrovirology · 2021Article
- Strategies for Targeting Retroviral Integration for Safer Gene Therapy: Advances and Challenges.Frontiers in molecular biosciences · 2021Review
- Cellular and molecular mechanisms of HIV-1 integration targeting.Cellular and molecular life sciences : CMLS · 2018Review
- Retroviral integrase protein and intasome nucleoprotein complex structures.World journal of biological chemistry · 2017Review
- Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization.Journal of virological methods · 2016Article
- Article
- The Competitive Interplay between Allosteric HIV-1 Integrase Inhibitor BI/D and LEDGF/p75 during the Early Stage of HIV-1 Replication Adversely Affects Inhibitor Potency.ACS chemical biology · 2016Article
- Production of unstable proteins through the formation of stable core complexes.Nature communications · 2016Article
- Sites of retroviral DNA integration: From basic research to clinical applications.Critical reviews in biochemistry and molecular biology · 2016Review
- DNA Physical Properties and Nucleosome Positions Are Major Determinants of HIV-1 Integrase Selectivity.PloS one · 2015Article
- HIV-1 integrase multimerization as a therapeutic target.Current topics in microbiology and immunology · 2015Review
- Structural Studies of the HIV-1 Integrase Protein: Compound Screening and Characterization of a DNA-Binding Inhibitor.PloS one · 2015Article
- Retroviral DNA Transposition: Themes and Variations.Microbiology spectrum · 2014Article
- The mechanism of H171T resistance reveals the importance of Nδ-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase.Retrovirology · 2014Article
- A critical role of the C-terminal segment for allosteric inhibitor-induced aberrant multimerization of HIV-1 integrase.The Journal of biological chemistry · 2014Article
- Rous sarcoma virus synaptic complex capable of concerted integration is kinetically trapped by human immunodeficiency virus integrase strand transfer inhibitors.The Journal of biological chemistry · 2014Article
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9 authors.
Funding
Abstract
A tetramer of HIV-1 integrase (IN) stably associates with the viral DNA ends to form a fully functional concerted integration intermediate. LEDGF/p75, a key cellular binding partner of the lentiviral enzyme, also stabilizes a tetrameric form of IN. However, functional assays have indicated the importance of the order of viral DNA and LEDGF/p75 addition to IN for productive concerted integration. Here, we employed Förster Resonance Energy Transfer (FRET) to monitor assembly of individual IN subunits into tetramers in the presence of viral DNA and LEDGF/p75. The IN-viral DNA and IN-LEDGF/p75 complexes yielded significantly different FRET values suggesting two distinct IN conformations in these complexes. Furthermore, the order of addition experiments indicated that FRET for the preformed IN-viral DNA complex remained unchanged upon its subsequent binding to LEDGF/p75, whereas pre-incubation of LEDGF/p75 and IN followed by addition of viral DNA yielded FRET very similar to the IN-LEDGF/p75 complex. These findings provide new insights into the structural organization of IN subunits in functional concerted integration intermediates and suggest that differential multimerization of IN in the presence of various ligands could be exploited as a plausible therapeutic target for development of allosteric inhibitors.
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