Journal Article

FZJ-2012-01057

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png HIV-1 Tat Binding to PCAF Bromodomain: Structural Determinants from Computational Methods

Quy, V. C. (Corresponding author)GRS* ; Pantano, S. ; Rossetti, G.FZJ* ; Giacca, M. ; Carloni, P. (Corresponding Author)FZJ*

2012
MDPI Basel

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Please use a persistent id in citations: http://hdl.handle.net/2128/4900  http://hdl.handle.net/2128/8842  doi:10.3390/biology1020277

Abstract: The binding between the HIV-1 trans-activator of transcription (Tat) and p300/(CREB-binding protein)-associated factor (PCAF) bromodomain is a crucial step in the HIV-1 life cycle. However, the structure of the full length acetylated Tat bound to PCAF has not been yet determined experimentally. Acetylation of Tat residues can play a critical role in enhancing HIV-1 transcriptional activation. Here, we have combined a fully flexible protein-protein docking approach with molecular dynamics simulations to predict the structural determinants of the complex for the common HIV-1BRU variant. This model reproduces all the crucial contacts between the Tat peptide 46SYGR(AcK)KRRQRC56 and the PCAF bromodomain previously reported by NMR spectroscopy. Additionally, inclusion of the entire Tat protein results in additional contact points at the protein-protein interface. The model is consistent with the available experimental data reported and adds novel information to our previous structural predictions of the PCAF bromodomain in complex with the rare HIVZ2 variant, which was obtained with a less accurate computational method. This improved characterization of Tat.PCAF bromodomain binding may help in defining the structural determinants of other protein interactions involving lysine acetylation.

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Contributing Institute(s):

1. Jülich Supercomputing Center (JSC)
2. Computational Biomedicine (IAS-5)
3. GRS (GRS)

Research Program(s):

1. 411 - Computational Science and Mathematical Methods (POF2-411) (POF2-411)

Appears in the scientific report 2012

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