Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain

Shiraz Mujtaba, Yan He, Lei Zeng, Amjad Farooq, Justin E. Carlson, Melanie Ott, Eric Verdin, Ming Ming Zhou

Research output: Contribution to journalArticle

191 Citations (Scopus)

Abstract

The human immunodeficiency virus type 1 (HIV-1) trans-activator protein Tat stimulates transcription of the integrated HIV-1 genome and promotes viral replication in infected cells. Tat transactivation activity is dependent on lysine acetylation and its association with nuclear histone acetyltransferases p300/CBP (CREB binding protein) and p300/CBP-associated factor (PCAF). Here, we show that the bromodomain of PCAF binds specifically to HIV-1 Tat acetylated at lysine 50 and that this interaction competes effectively against HIV-1 TAR RNA binding to the lysine-acetylated Tat. The three-dimensional solution structure of the PCAF bromodomain in complex with a lysine 50-acetylated Tat peptide together with biochemical analyses provides the structural basis for the specificity of this molecular recognition and reveals insights into the differences in ligand selectivity of bromodomains.

Original languageEnglish
Pages (from-to)575-586
Number of pages12
JournalMolecular Cell
Volume9
Issue number3
DOIs
StatePublished - Apr 15 2002
Externally publishedYes

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Lysine
HIV-1
CREB-Binding Protein
tat Gene Products
Histone Acetyltransferases
Trans-Activators
Viral Genome
Acetylation
Transcriptional Activation
RNA
Ligands
Peptides
p300-CBP-associated factor

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain. / Mujtaba, Shiraz; He, Yan; Zeng, Lei; Farooq, Amjad; Carlson, Justin E.; Ott, Melanie; Verdin, Eric; Zhou, Ming Ming.

In: Molecular Cell, Vol. 9, No. 3, 15.04.2002, p. 575-586.

Research output: Contribution to journalArticle

Mujtaba, S, He, Y, Zeng, L, Farooq, A, Carlson, JE, Ott, M, Verdin, E & Zhou, MM 2002, 'Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain', Molecular Cell, vol. 9, no. 3, pp. 575-586. https://doi.org/10.1016/S1097-2765(02)00483-5
Mujtaba, Shiraz ; He, Yan ; Zeng, Lei ; Farooq, Amjad ; Carlson, Justin E. ; Ott, Melanie ; Verdin, Eric ; Zhou, Ming Ming. / Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain. In: Molecular Cell. 2002 ; Vol. 9, No. 3. pp. 575-586.
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AU - Verdin, Eric

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