ArticleThe Journal of biological chemistry2008
Dynamic modulation of HIV-1 integrase structure and function by cellular lens epithelium-derived growth factor (LEDGF) protein.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 127 citations in OpenAlex.
- Identifying Conserved Regions in HIV-1 Proteins by Entropy Analysis of Sequence Variability.International journal of molecular sciences · 2026Article
- Article
- Retroviral intasome architecture shapes the dynamics of target DNA search and integration.PLoS pathogens · 2026Article
- Oligomeric HIV-1 integrase structures reveal functional plasticity for intasome assembly and RNA binding.Nature communications · 2025Article
- Brief Histories of Retroviral Integration Research and Associated International Conferences.Viruses · 2024Review
- Biological and Structural Analyses of New Potent Allosteric Inhibitors of HIV-1 Integrase.Antimicrobial agents and chemotherapy · 2023Article
- Structure of a HIV-1 IN-Allosteric inhibitor complex at 2.93 Å resolution: Routes to inhibitor optimization.PLoS pathogens · 2023Article
- The Drug-Induced Interface That Drives HIV-1 Integrase Hypermultimerization and Loss of Function.mBio · 2023Article
- Implications of Fragment-Based Drug Discovery in Tuberculosis and HIV.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Article
- Allosteric Integrase Inhibitor Influences on HIV-1 Integration and Roles of LEDGF/p75 and HDGFL2 Host Factors.Viruses · 2022Article
- Multimodal Functionalities of HIV-1 Integrase.Viruses · 2022Review
- Article
- HIV-1 integrase binding to genomic RNA 5'-UTR induces local structural changes in vitro and in virio.Retrovirology · 2021Article
- Retroviral integrase: Structure, mechanism, and inhibition.The Enzymes · 2021Article
- Strategies for Targeting Retroviral Integration for Safer Gene Therapy: Advances and Challenges.Frontiers in molecular biosciences · 2021Review
- Integrase-RNA interactions underscore the critical role of integrase in HIV-1 virion morphogenesis.eLife · 2020Article
- Going beyond Integration: The Emerging Role of HIV-1 Integrase in Virion Morphogenesis.Viruses · 2020Review
- Influence of the amino-terminal sequence on the structure and function of HIV integrase.Retrovirology · 2020Article
- A Peptide Derived from Lens Epithelium-Derived Growth Factor Stimulates HIV-1 DNA Integration and Facilitates Intasome Structural Studies.Journal of molecular biology · 2020Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The mandatory integration of the reverse-transcribed HIV-1 genome into host chromatin is catalyzed by the viral protein integrase (IN), and IN activity can be regulated by numerous viral and cellular proteins. Among these, LEDGF has been identified as a cellular cofactor critical for effective HIV-1 integration. The x-ray crystal structure of the catalytic core domain (CCD) of IN in complex with the IN binding domain (IBD) of LEDGF has furthermore revealed essential protein-protein contacts. However, mutagenic studies indicated that interactions between the full-length proteins were more extensive than the contacts observed in the co-crystal structure of the isolated domains. Therefore, we have conducted detailed biochemical characterization of the interactions between full-length IN and LEDGF. Our results reveal a highly dynamic nature of IN subunit-subunit interactions. LEDGF strongly stabilized these interactions and promoted IN tetramerization. Mass spectrometric protein footprinting and molecular modeling experiments uncovered novel intra- and inter-protein-protein contacts in the full-length IN-LEDGF complex that lay outside of the observable IBD-CCD structure. In particular, our studies defined the IN tetramer interface important for enzymatic activities and high affinity LEDGF binding. These findings provide new insight into how LEDGF modulates HIV-1 IN structure and function, and highlight the potential for exploiting the highly dynamic structure of multimeric IN as a novel therapeutic target.
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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.