ArticlePloS one2013
Structural and functional role of INI1 and LEDGF in the HIV-1 preintegration complex.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016Pooled it
- Towards a phylogenetically informed approach to solving protein-protein interactions.Biochemical Society transactions · 2025Review
- TAR RNA Mimicry of INI1 and Its Influence on Non-Integration Function of HIV-1 Integrase.Viruses · 2025Review
- HIV-1 capsid and viral DNA integration.mBio · 2024Review
- Complex Relationships between HIV-1 Integrase and Its Cellular Partners.International journal of molecular sciences · 2022Review
- Review
- Efficient production of protein complexes in mammalian cells using a poxvirus vector.PloS one · 2022Article
- A Coil-to-Helix Transition Serves as a Binding Motif for hSNF5 and BAF155 Interaction.International journal of molecular sciences · 2020Article
- Two-long terminal repeat (LTR) DNA circles are a substrate for HIV-1 integrase.The Journal of biological chemistry · 2019Article
- An Essential Role of INI1/hSNF5 Chromatin Remodeling Protein in HIV-1 Posttranscriptional Events and Gag/Gag-Pol Stability.Journal of virology · 2016Article
- Computational modeling of Repeat1 region of INI1/hSNF5: An evolutionary link with ubiquitin.Protein science : a publication of the Protein Society · 2016Article
- Production of unstable proteins through the formation of stable core complexes.Nature communications · 2016Article
- Different Pathways Leading to Integrase Inhibitors Resistance.Frontiers in microbiology · 2016Review
- Impact of Chromatin on HIV Replication.Genes · 2015Review
- DNA Physical Properties and Nucleosome Positions Are Major Determinants of HIV-1 Integrase Selectivity.PloS one · 2015Article
- The dynamics of interconverting D- and E-forms of the HIV-1 integrase N-terminal domain.European biophysics journal : EBJ · 2014Article
- Repair of oxidative DNA base damage in the host genome influences the HIV integration site sequence preference.PloS one · 2014Article
- Transgenic expression of the human LEDGF/p75 gene relieves the species barrier against HIV-1 infection in mouse cells.Frontiers in microbiology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Integration of the HIV-1 cDNA into the human genome is catalyzed by the viral integrase (IN) protein. Several studies have shown the importance of cellular cofactors that interact with integrase and affect viral integration and infectivity. In this study, we produced a stable complex between HIV-1 integrase, viral U5 DNA, the cellular cofactor LEDGF/p75 and the integrase binding domain of INI1 (INI1-IBD), a subunit of the SWI/SNF chromatin remodeling factor. The stoichiometry of the IN/LEDGF/INI1-IBD/DNA complex components was found to be 4/2/2/2 by mass spectrometry and Fluorescence Correlation Spectroscopy. Functional assays showed that INI1-IBD inhibits the 3' processing reaction but does not interfere with specific viral DNA binding. Integration assays demonstrate that INI1-IBD decreases the amount of integration events but inhibits by-product formation such as donor/donor or linear full site integration molecules. Cryo-electron microscopy locates INI1-IBD within the cellular DNA binding site of the IN/LEDGF complex, constraining the highly flexible integrase in a stable conformation. Taken together, our results suggest that INI1 could stabilize the PIC in the host cell, by maintaining integrase in a stable constrained conformation which prevents non-specific interactions and auto integration on the route to its integration site within nucleosomes, while LEDGF organizes and stabilizes an active integrase tetramer suitable for specific vDNA integration. Moreover, our results provide the basis for a novel type of integrase inhibitor (conformational inhibitor) representing a potential new strategy for use in human therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.