Crystal structure of HIV-1 Tat complexed with human P-TEFb

Tahir H Tahirov, Nigar D. Babayeva, Katayoun Varzavand, Jeffrey J. Cooper, Stanley C. Sedore, David H. Price

Research output: Contribution to journalArticle

182 Citations (Scopus)

Abstract

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 cells 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 TatP-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 TatP-TEFb complex and block HIV replication.

Original languageEnglish (US)
Pages (from-to)747-751
Number of pages5
JournalNature
Volume465
Issue number7299
DOIs
StatePublished - Jun 10 2010

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Positive Transcriptional Elongation Factor B
HIV-1
Cyclin T
HIV
RNA Polymerase II
Viral Proteins
Virus Replication
Transcription Factors
Genome
Messenger RNA

ASJC Scopus subject areas

  • General

Cite this

Tahirov, T. H., Babayeva, N. D., Varzavand, K., Cooper, J. J., Sedore, S. C., & Price, D. H. (2010). Crystal structure of HIV-1 Tat complexed with human P-TEFb. Nature, 465(7299), 747-751. https://doi.org/10.1038/nature09131

Crystal structure of HIV-1 Tat complexed with human P-TEFb. / Tahirov, Tahir H; Babayeva, Nigar D.; Varzavand, Katayoun; Cooper, Jeffrey J.; Sedore, Stanley C.; Price, David H.

In: Nature, Vol. 465, No. 7299, 10.06.2010, p. 747-751.

Research output: Contribution to journalArticle

Tahirov, TH, Babayeva, ND, Varzavand, K, Cooper, JJ, Sedore, SC & Price, DH 2010, 'Crystal structure of HIV-1 Tat complexed with human P-TEFb', Nature, vol. 465, no. 7299, pp. 747-751. https://doi.org/10.1038/nature09131
Tahirov TH, Babayeva ND, Varzavand K, Cooper JJ, Sedore SC, Price DH. Crystal structure of HIV-1 Tat complexed with human P-TEFb. Nature. 2010 Jun 10;465(7299):747-751. https://doi.org/10.1038/nature09131
Tahirov, Tahir H ; Babayeva, Nigar D. ; Varzavand, Katayoun ; Cooper, Jeffrey J. ; Sedore, Stanley C. ; Price, David H. / Crystal structure of HIV-1 Tat complexed with human P-TEFb. In: Nature. 2010 ; Vol. 465, No. 7299. pp. 747-751.
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