ArticleNucleic acids research2013
Structural basis for high-affinity binding of LEDGF PWWP to mononucleosomes.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers.
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Who cites it
131 citing papers in PubMed, 204 citations in OpenAlex.
- Core nucleosomes are refractory to lentiviral DNA integration.Nature communications · 2026Article
- The LEDGIN GS-9822 inhibits HIV-2 infection and enhances HIV-2 latency.Microbiology spectrum · 2026Article
- High-Affinity Nanobody Against the LEDGF PWWP Domain Inhibits Chromatin Binding In Vitro.Biomolecules · 2026Article
- Block-and-Lock Approaches for HIV Cure: Mechanistic Insights, Challenges, and Emerging Role of CPSF6.International journal of molecular sciences · 2026Review
- Relationship between the distribution of LEDGF along genes and positions of HIV-1 DNA integration.mBio · 2026Article
- Metabolic oxidoreductases: central regulators of the epigenetic landscapes in stemness.Experimental & molecular medicine · 2026Review
- KMT2A-rearranged leukemia: from mechanism to drug development.Experimental hematology · 2025Review
- Co-targeting menin and LSD1 dismantles oncogenic programs and restores differentiation in MLL-rearranged AML.bioRxiv : the preprint server for biology · 2025Article
- LEDGF Binds H3R17me2a Promoting De Novo Nucleotide Biosynthesis in SETD2 Mutant Clear Cell Renal Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Structural basis of thymidine-rich DNA recognition by Drosophila P75 PWWP domain.Communications biology · 2025Article
- Facile preparation of sulfonium peptide and protein probes for selective crosslinking of methyllysine readers.Chemical science · 2025Article
- A dual role for PSIP1/LEDGF in T cell acute lymphoblastic leukemia.Science advances · 2024Article
- DNMT3B PWWP mutations cause hypermethylation of heterochromatin.EMBO reports · 2024Article
- Article
- The Impact of Lens Epithelium-Derived Growth Factor p75 Dimerization on Its Tethering Function.Cells · 2024Article
- Multivalency of nucleosome recognition by LEDGF.Nucleic acids research · 2023Article
- The HIV-2 OGH double reporter virus shows that HIV-2 is less cytotoxic and less sensitive to reactivation from latency than HIV-1 in cell culture.Journal of virus eradication · 2023Article
- GS-9822, a preclinical LEDGIN candidate, displays a block-and-lock phenotype in cell culture.Antimicrobial agents and chemotherapy · 2023Article
- Epigenetic and chromosomal features drive transposon insertion in Drosophila melanogaster.Nucleic acids research · 2023Article
- Histone Readers and Their Roles in Cancer.Cancer treatment and research · 2023Article
71 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Lens epithelium-derived growth factor (LEDGF/p75) tethers lentiviral preintegration complexes (PICs) to chromatin and is essential for effective HIV-1 replication. LEDGF/p75 interactions with lentiviral integrases are well characterized, but the structural basis for how LEDGF/p75 engages chromatin is unknown. We demonstrate that cellular LEDGF/p75 is tightly bound to mononucleosomes (MNs). Our proteomic experiments indicate that this interaction is direct and not mediated by other cellular factors. We determined the solution structure of LEDGF PWWP and monitored binding to the histone H3 tail containing trimethylated Lys36 (H3K36me3) and DNA by NMR. Results reveal two distinct functional interfaces of LEDGF PWWP: a well-defined hydrophobic cavity, which selectively interacts with the H3K36me3 peptide and adjacent basic surface, which non-specifically binds DNA. LEDGF PWWP exhibits nanomolar binding affinity to purified native MNs, but displays markedly lower affinities for the isolated H3K36me3 peptide and DNA. Furthermore, we show that LEDGF PWWP preferentially and tightly binds to in vitro reconstituted MNs containing a tri-methyl-lysine analogue at position 36 of H3 and not to their unmodified counterparts. We conclude that cooperative binding of the hydrophobic cavity and basic surface to the cognate histone peptide and DNA wrapped in MNs is essential for high-affinity binding to chromatin.
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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.