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Crystal structure of HIV-1 Tat complexed with human P-TEFb
Open accessAbstract
Regulation of the expression of the human immunodeficiency virus (HIV) genome is accomplished in large part by controlling transcription elongation. The viral protein Tat hijacks the host cell's RNA polymerase II elongation control machinery through interaction with the positive transcription elongation factor, P-TEFb, and directs the factor to promote productive elongation of HIV mRNA. Here we describe the crystal structure of the Tat.P-TEFb complex containing HIV-1 Tat, human Cdk9 (also known as CDK9), and human cyclin T1 (also known as CCNT1). Tat adopts a structure complementary to the surface of P-TEFb and makes extensive contacts, mainly with the cyclin T1 subunit of P-TEFb, but also with the T-loop of the Cdk9 subunit. The structure provides a plausible explanation for the tolerance of Tat to sequence variations at certain sites. Importantly, Tat induces significant conformational changes in P-TEFb. This finding lays a foundation for the design of compounds that would specifically inhibit the Tat.P-TEFb complex and block HIV replication.
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“Following the Tat–TAR interaction, the host super elongation complex, which includes the cellular positive transcription elongation factor p-TEFb and polymerase-associated factor 1 (PAF-1), is recruited to further boost transcription, significantly increasing the production of viral RNA transcripts (Fig. 8A) (Peterlin and Price 2006, Tahirov et al. 2010, Gu et al. 2014).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Tahirov et al. 2010
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Cites
[20] Processing of X-ray diffraction data collected in oscillation mode
Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination
Brünger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse‐Kunstleve, R. W., Jiang, J., Kuszewski, J. J., Nilges, M., Pannu, N., et al. (1998) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444998003254 · Cited by 15,723
WebLogo: A Sequence Logo Generator: Figure 1Preprint
Crooks, G. E., Hon, G. C., Chandonia, J., & Brenner, S. E. (2004) · Genome Research · doi:10.1101/gr.849004 · Cited by 12,480
Controlling the elongation phase of transcription with P-TEFb
Peterlin, B. M., & Price, D. H. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.06.014 · Cited by 1,144
Self-citationCrystal structure of the p27Kip1 cyclin-dependent-kinase inibitor bound to the cyclin A–Cdk2 complex
Russo, A. A., Jeffrey, P. D., Patten, A. K., Massagué, J., & Pavletich, N. P. (1996) · Nature · doi:10.1038/382325a0 · Cited by 899
Pavletich, N. P. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.2640 · Cited by 746
Transcription elongation factor P-TEFb is required for HIV-1 Tat transactivation in vitroPreprint
Zhu, Y., Peery, T., Peng, J., Ramanathan, Y., Marshall, N. F., Marshall, T. K., Amendt, B. A., Mathews, M. B., & Price, D. H. (1997) · Genes & Development · doi:10.1101/gad.11.20.2622 · Cited by 700
Self-citationControl of RNA Polymerase II Elongation Potential by a Novel Carboxyl-terminal Domain Kinase
Marshall, N. F., Peng, J., Xie, Z., & Price, D. H. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.43.27176 · Cited by 662
Self-citationGlobal and regional distribution of HIV-1 genetic subtypes and recombinants in 2004
Hemelaar, J., Gouws, E., Ghys, P. D., & Osmanov, S. (2006) · AIDS · doi:10.1097/01.aids.0000247564.73009.bc · Cited by 627
Flavopiridol Inactivates P-TEFb and Blocks Most RNA Polymerase II Transcription in Vivo
Chao, S., & Price, D. H. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102306200 · Cited by 623
Self-citationP-TEFb kinase is required for HIV Tat transcriptional activation in vivo and in vitroPreprint
Mancebo, H. S. Y., Lee, G., Flygare, J. A., Tomassini, J. E., Luu, P., Zhu, Y., Peng, J., Blau, C., Hazuda, D. J., Price, D. H., et al. (1997) · Genes & Development · doi:10.1101/gad.11.20.2633 · Cited by 546
Self-citationIdentification of multiple cyclin subunits of human P-TEFb.Preprint
Peng, J.-M., Zhu, Y., Milton, J. T., & Price, D. (1998) · Genes & Development · doi:10.1101/gad.12.5.755 · Cited by 531
Self-citationYik, J. H. N., Chen, R., Nishimura, R., Jennings, J. L., Link, A. J., & Zhou, Q. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00388-5 · Cited by 464
Garber, M. E., Wei, P., KewalRamani, V. N., Mayall, T. P., Herrmann, C. H., Rice, A. P., Littman, D. R., & Jones, K. A. (1998) · Genes & Development · doi:10.1101/gad.12.22.3512 · Cited by 430
Structural and functional characterization of human immunodeficiency virus tat protein
Ruben, S. M., Perkins, A., Purcell, R. D., Joung, K., Sia, R. A. L., Burghoff, R. L., Haseltine, W. A., & Rosen, C. A. (1989) · Journal of Virology · doi:10.1128/jvi.63.1.1-8.1989 · Cited by 424
Multifaceted Activities of the HIV-1 Transactivator of Transcription, Tat
Jeang, K., Xiao, H., & Rich, E. A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.41.28837 · Cited by 416
Structural basis for transcription elongation by bacterial RNA polymerase
Vassylyev, D. G., Vassylyeva, M. N., Perederina, A. A., Tahirov, T. H., & Artsimovitch, I. (2007) · Nature · doi:10.1038/nature05932 · Cited by 409
Self-citationBaumli, S., Lolli, G., Lowe, E. D., Troiani, S., Rusconi, L., Bullock, A. N., Debreczeni, J. E., Knapp, S., & Johnson, L. N. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.121 · Cited by 357
Zhou, Q., & Yik, J. H. N. (2006) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00011-06 · Cited by 269
Zhou, M., Halanski, M. A., Radonovich, M. F., Kashanchi, F., Peng, J., Price, D. H., & Brady, J. N. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.14.5077-5086.2000 · Cited by 261
Self-citationBieniasz, P. D., Grdina, T. A., Bogerd, H. P., & Cullen, B. R. (1998) · The EMBO Journal · doi:10.1093/emboj/17.23.7056 · Cited by 260
Multiple functional domains of Tat, thetrans-activator of HIV-1, defined by mutational analysis
Kuppuswamy, M. N., Subramanian, T., Srinivasan, A., & Chinnadurai, G. (1989) · Nucleic Acids Research · doi:10.1093/nar/17.9.3551 · Cited by 252
MAQ1 and 7SK RNA Interact with CDK9/Cyclin T Complexes in a Transcription-Dependent Manner
Michels, A. A., Nguyen, V. T., Fraldi, A., Labas, V., Edwards, M., Bonnet, F., Lania, L., & Bensaude, O. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.14.4859-4869.2003 · Cited by 230
Cyclin K Functions as a CDK9 Regulatory Subunit and Participates in RNA Polymerase II Transcription
Fu, T.-J., Peng, J., Lee, G., Price, D. H., & Flores, O. A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.49.34527 · Cited by 224
Self-citationLi, Q., Price, J. P., Byers, S. A., Cheng, D., Peng, J., & Price, D. H. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502712200 · Cited by 215
Self-citationSpecific versus non-specific contacts in protein crystals
Janin, J. (1997) · Nature Structural Biology · doi:10.1038/nsb1297-973 · Cited by 206
Tat competes with HEXIM1 to increase the active pool of P-TEFb for HIV-1 transcription
Barborič, M., Yik, J. H. N., Czudnochowski, N., Yang, Z., Chen, R., Contreras, X., Geyer, M., Peterlin, B. M., & Zhou, Q. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm063 · Cited by 197
The Remarkable Frequency of Human Immunodeficiency Virus Type 1 Genetic Recombination
Onafuwa-Nuga, A., & Telesnitsky, A. (2009) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00012-09 · Cited by 191
Chen, R., Yang, Z., & Zhou, Q. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310044200 · Cited by 166
Fujinaga, K., Cujec, T. P., Peng, J., Garriga, J., Price, D. H., Graña, X., & Peterlin, B. M. (1998) · Journal of Virology · doi:10.1128/jvi.72.9.7154-7159.1998 · Cited by 165
Self-citationSedore, S. C., Byers, S. A., Biglione, S., Price, J. P., Maury, W. J., & Price, D. H. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm443 · Cited by 157
Self-citationIppolito, J. A., & Steitz, T. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.17.9819 · Cited by 141
Rice, A. P., & Carlotti, F. (1990) · Journal of Virology · doi:10.1128/jvi.64.4.1864-1868.1990 · Cited by 99
Campbell, G. R., & Loret, E. P. (2009) · Retrovirology · doi:10.1186/1742-4690-6-50 · Cited by 98
Jancarik, J., Pufan, R., Hong, C., Kim, S., & Kim, R. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904010972 · Cited by 94
TAR RNA loop: A scaffold for the assembly of a regulatory switch in HIV replication
Richter, S. N., Ping, Y., & Rana, T. M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122119999 · Cited by 84
Structural insights into the Cyclin T1–Tat–TAR RNA transcription activation complex from EIAV
Anand, K., Schulte, A., Vogel‐Bachmayr, K., Scheffzek, K., & Geyer, M. (2008) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1513 · Cited by 82
Wimmer, J., Fujinaga, K., Taube, R., Cujec, T. P., Zhu, Y., Peng, J., Price, D. H., & Peterlin, B. M. (1999) · Virology · doi:10.1006/viro.1998.9589 · Cited by 81
Self-citationHIV-1 Tat Interacts with Cyclin T1 to Direct the P-TEFb CTD Kinase Complex to TAR RNAPreprint
Garber, M. E., Wei, P., & Jones, K. A. (1998) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1998.63.371 · Cited by 78
Tat acetylation modulates assembly of a viral-host RNA–protein transcription complex
D’Orso, I., & Frankel, A. D. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900012106 · Cited by 67
Taube, R., Fujinaga, K., Irwin, D., Wimmer, J., Geyer, M., & Peterlin, B. M. (2000) · Journal of Virology · doi:10.1128/jvi.74.2.892-898.2000 · Cited by 37
Michels, A. A., & Bensaude, O. (2008) · Biotechnology Journal · doi:10.1002/biot.200800104 · Cited by 34
Moving Forward in HIV Vaccine Development
Letvin, N. L. (2009) · Science · doi:10.1126/science.1183278 · Cited by 31
Sadaie, M. R., Mukhopadhyaya, R., BENAISSA, Z. N., Pavlakis, G. N., & Wong‐Staal, F. (1990) · AIDS Research and Human Retroviruses · doi:10.1089/aid.1990.6.1257 · Cited by 23
Tahirov, T. H., Oki, H., Tomitake Tsukihara, A., Ogasahara, K., Yutani, K., Libeu, C. P., Izu, Y., Tsunasawa, S., & Kato, I. (1998) · Journal of Structural Biology · doi:10.1006/jsbi.1997.3940 · Cited by 21
Self-citationRole of the HIV-1 Positive Elongation Factor P-TEFb and Inhibitors Thereof
Wang, Y., Liu, X., & Clercq, E. D. (2009) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557510909030379 · Cited by 19
Derse, D., & Newbold, S. H. (1993) · Virology · doi:10.1006/viro.1993.1291 · Cited by 18
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Metadata
- Authors
- Tahirov, T. H., Babayeva, N. D., Varzavand, K., Cooper, J. J., Sedore, S. C., & Price, D. H.
- Affiliations
- University of Nebraska Medical Center (US)
- University of Iowa (US)
- Corresponding author
- Tahirov, Tahir H.
- Venue
- Nature
- Published
- 2010-06
- Volume
- 465
- Issue
- 7299
- Pages
- 747-751
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2885016
- OpenAlex
- W2127284613
- Cited by
- 314
- References
- 47
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 13 · 2023: 7 · 2022: 13 · 2021: 10 · 2020: 16 · 2019: 15 · 2018: 25 · 2017: 27 · 2016: 27 · 2015: 24 · 2014: 23 · 2013: 30 · 2012: 28
- FWCI
- 11.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (P30CA036727)
- National Institute of General Medical Sciences (R01GM035500, R01GM082923, GM-35500, GM082923)
- National Institute of Allergy and Infectious Diseases (AI074392, R21AI074392, R33AI074392)
- National Center for Research Resources (RR 15301, P41RR015301)
- Basic Energy Sciences
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- HIV-1 Tat protein, P-TEFb, CDK9, cyclin T1, transcription elongation, protein-protein interaction, conformational change, HIV replication, antiviral drug targets
- MeSH terms
- Adenosine Triphosphate, Amino Acid Sequence, Animals, Binding Sites, Enzyme Activation, Humans, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Conformation, HIV-1, Crystallography, X-Ray, Cyclin-Dependent Kinase 9, Positive Transcriptional Elongation Factor B, tat Gene Products, Human Immunodeficiency Virus, Cyclin T
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