ArticleCell cycle (Georgetown, Tex.)2014
Crystal structure of HIV-1 Tat complexed with human P-TEFb and AFF4.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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Who cites it
43 citing papers in PubMed, 58 citations in OpenAlex.
- Cell heterogeneity contributes to the variable response of HIV-1 to latency-reversing agents.Science advances · 2026Article
- Quantitative limits of host-driven HIV transcription and host gene control by the viral transactivator Tat.Nucleic acids research · 2026Article
- Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication.FEMS microbiology reviews · 2026Review
- Interactome of the HIV-1 proteome and human host RNA.EMBO reports · 2024Article
- Review
- The Biological Significance of AFF4: Promoting Transcription Elongation, Osteogenic Differentiation and Tumor Progression.Combinatorial chemistry & high throughput screening · 2024Review
- HIV-1 Transcription Inhibition Using Small RNA-Binding Molecules.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Accurate Prediction of Transcriptional Activity of Single Missense Variants in HIV Tat with Deep Learning.International journal of molecular sciences · 2023Article
- Enhancing HIV-1 latency reversal through regulating the elongating RNA Pol II pause-release by a small-molecule disruptor of PAF1C.Science advances · 2023Article
- Review
- RNA-Binding Macrocyclic Peptides.Frontiers in molecular biosciences · 2022Review
- The TAR binding dynamics and its implication in Tat degradation mechanism.Biophysical journal · 2021Article
- Functional Relevance of the Interaction between Human Cyclins and the Cytomegalovirus-Encoded CDK-Like Protein Kinase pUL97.Viruses · 2021Article
- Structure, function and inhibition of critical protein-protein interactions involving mixed lineage leukemia 1 and its fusion oncoproteins.Journal of hematology & oncology · 2021Review
- Discriminative SKP2 Interactions with CDK-Cyclin Complexes Support a Cyclin A-Specific Role in p27KIP1 Degradation.Journal of molecular biology · 2021Article
- Structure of the super-elongation complex subunit AFF4 C-terminal homology domain reveals requirements for AFF homo- and heterodimerization.The Journal of biological chemistry · 2019Article
- Face-time with TAR: Portraits of an HIV-1 RNA with diverse modes of effector recognition relevant for drug discovery.The Journal of biological chemistry · 2019Review
- Genetic variation and function of the HIV-1 Tat protein.Medical microbiology and immunology · 2019Review
- An ultra-high affinity ligand of HIV-1 TAR reveals the RNA structure recognized by P-TEFb.Nucleic acids research · 2019Article
- Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Developing anti-viral therapies targeting HIV-1 transcription has been hampered by the limited structural knowledge of the proteins involved. HIV-1 hijacks the cellular machinery that controls RNA polymerase II elongation through an interaction of HIV-1 Tat with the positive transcription elongation factor P-TEFb, which interacts with an AF4 family member (AFF1/2/3/4) in the super elongation complex (SEC). Because inclusion of Tat•P-TEFb into the SEC is critical for HIV transcription, we have determined the crystal structure of the Tat•AFF4•P-TEFb complex containing HIV-1 Tat (residues 1-48), human Cyclin T1 (1-266), human Cdk9 (7-332), and human AFF4 (27-69). Tat binding to AFF4•P-TEFb causes concerted structural changes in AFF4 via a shift of helix H5' of Cyclin T1 and the α-3 10 helix of AFF4. The interaction between Tat and AFF4 provides structural constraints that explain tolerated Tat mutations. Analysis of the Tat-binding surface of AFF4 coupled with modeling of all other AF4 family members suggests that AFF1 and AFF4 would be preferred over AFF2 or AFF3 for interaction with Tat•P-TEFb. The structure establishes that the Tat-TAR recognition motif (TRM) in Cyclin T1 interacts with both Tat and AFF4, leading to the exposure of arginine side chains for binding to TAR RNA. Furthermore, modeling of Tat Lys28 acetylation suggests that the acetyl group would be in a favorable position for H-bond formation with Asn257 of TRM, thereby stabilizing the TRM in Cyclin T1, and provides a structural basis for the modulation of TAR RNA binding by acetylation of Tat Lys28.
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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.