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

doi:10.1038/nature09131

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

Journal article

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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 and David H Price

Nature (London), Vol.465(7299), pp.747-751

06/10/2010

DOI: 10.1038/nature09131

PMCID: PMC2885016

PMID: 20535204

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https://www.ncbi.nlm.nih.gov/pmc/articles/2885016View

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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 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, and human Cyclin T1. 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.

Details

Title: Subtitle: Crystal structure of HIV-1 Tat complexed with human P-TEFb
Creators: Tahir H Tahirov - Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-7696, USA
Nigar D Babayeva - Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-7696, USA
Katayoun Varzavand - Biochemistry Department, University of Iowa, Iowa City, IA 52242
Jeffrey J Cooper - Biochemistry Department, University of Iowa, Iowa City, IA 52242
Stanley C Sedore - Biochemistry Department, University of Iowa, Iowa City, IA 52242
David H Price - Biochemistry Department, University of Iowa, Iowa City, IA 52242
Resource Type: Journal article
Publication Details: Nature (London), Vol.465(7299), pp.747-751
DOI: 10.1038/nature09131
PMID: 20535204
PMCID: PMC2885016
NLM abbreviation: Nature
ISSN: 0028-0836
eISSN: 1476-4687
Language: English
Date published: 06/10/2010
Academic Unit: The University of Iowa Institute for Vision Research; Biochemistry and Molecular Biology
Record Identifier: 9984024561102771

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