HIV-1 Tat recruits transcription elongation factors dispersed along a flexible AFF4 scaffold
Open accessAbstract
The HIV-1 Tat protein stimulates viral gene expression by recruiting human transcription elongation complexes containing P-TEFb, AFF4, ELL2, and ENL or AF9 to the viral promoter, but the molecular organization of these complexes remains unknown. To establish the overall architecture of the HIV-1 Tat elongation complex, we mapped the binding sites that mediate complex assembly in vitro and in vivo. The AFF4 protein emerges as the central scaffold that recruits other factors through direct interactions with short hydrophobic regions along its structurally disordered axis. Direct binding partners CycT1, ELL2, and ENL or AF9 act as bridging components that link this complex to two major elongation factors, P-TEFb and the PAF complex. The unique scaffolding properties of AFF4 allow dynamic and flexible assembly of multiple elongation factors and connect the components not only to each other but also to a larger network of transcriptional regulators.
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Recruitment of the PAF complex via a flexible AFF4 scaffold ensures transcript elongation, providing the structural basis for the transition from pausing to active elongation.
“During this process, the recruitment of the PAF complex via a flexible AFF4 scaffold ensures transcript elongation, providing the structural basis for the transition from pausing to active elongation (Feinberg et al. 1991, Chou et al. 2013, Vos et al. 2020).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Chou et al. 2013
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“With four, three, and two human homologs of AFF4, ELL, and ENL, respectively, as well as posttranslational modifications of the subunits, including P-TEFb (14, 43, 44), these data demonstrate the potential for considerable variability in SEC composition.”
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Mechanisms of HIV transcriptional regulation by drugs of abuse
Tyagi, M., Bukrinsky, M., & L. Simon, G. (2016) · Current HIV Research · doi:10.2174/1570162x14666160324124736 · Cited by 42 · see citing works
Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication
Jehad, M. A., Ali, L. M., Pillai, V. N., Prabhu, S. G., Mustafa, F., & Rizvi, T. A. (2026) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuaf066 · Cited by 5 · see citing works
“During this process, the recruitment of the PAF complex via a flexible AFF4 scaffold ensures transcript elongation, providing the structural basis for the transition from pausing to active elongation (Feinberg et al. 1991 , Chou et al. 2013 , Vos et al. 2020 ).”
- Authors
- Chou, S., Upton, H., Bao, K., Schulze-Gahmen, U., Samelson, A. J., He, N., Nowak, A., Lu, H., Krogan, N. J., Zhou, Q., & Alber, T.
- Affiliations
- University of California, Berkeley (US)
- Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;
- QB3 (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-12-18
- Volume
- 110
- Issue
- 2
- Pages
- E123-31
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3545800
- OpenAlex
- W2124620363
- Cited by
- 93
- References
- 4
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 7 · 2023: 11 · 2022: 3 · 2021: 6 · 2020: 14 · 2019: 4 · 2018: 1 · 2017: 7 · 2016: 8 · 2015: 6 · 2014: 12 · 2013: 8
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- California HIV/AIDS Research Program
- National Institutes of Health (R01AI41757, R01AI41757-11)
- National Institute of General Medical Sciences (P50GM082250, P50 GM82250, T32GM007232)
- National Institute of Allergy and Infectious Diseases (R01AI41757-11, R01AI041757, R01AI095057, P30AI027763)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- HIV-1 Tat protein, transcription elongation, AFF4, P-TEFb, ELL2, ENL, AF9, PAF complex, protein complex formation, scaffold proteins, disordered protein regions, protein-protein interaction, viral gene expression, transcription factors
- MeSH terms
- Binding Sites, Circular Dichroism, Electrophoresis, Escherichia coli, HeLa Cells, Humans, Luciferases, Repressor Proteins, Blotting, Western, HIV-1, Gene Expression Regulation, Viral, Transcriptional Elongation Factors, Positive Transcriptional Elongation Factor B, Multiprotein Complexes, Immunoprecipitation, tat Gene Products, Human Immunodeficiency Virus, Cyclin T
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