@article{b028c051cbca4fdc80d2d5be6a14b219,
title = "Crystal structure of HIV-1 Tat complexed with human P-TEFb",
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.",
author = "Tahirov, {Tahir H.} and Babayeva, {Nigar D.} and Katayoun Varzavand and Cooper, {Jeffrey J.} and Sedore, {Stanley C.} and Price, {David H.}",
note = "Funding Information: Acknowledgements We thank J. Lovelace and G. E. Borgstahl for maintenance and management of the Eppley Institute{\textquoteright}s X-ray Crystallography facility; D. G. Vassylyev for the zonal scaling instruction files. This work is supported by the NIH grants GM35500 and AI074392 to D.H.P., by Nebraska Department of Health and Human Services grant LB506 and in part by NIH grant GM082923 to T.H.T. This work is also based on research conducted at the Advanced Photon Source on the Northeastern Collaborative Access Team beamlines, which are supported by award RR-15301 from the National Center for Research Resources at the National Institutes of Health. Use of the Advanced Photon Source is supported by the US Department of Energy, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. The Eppley Institute{\textquoteright}s X-ray Crystallography facility is supported by Cancer Center Support Grant P30CA036727.",
year = "2010",
month = jun,
day = "10",
doi = "10.1038/nature09131",
language = "English (US)",
volume = "465",
pages = "747--751",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Research",
number = "7299",
}