Next Article in Journal
Analyzing the microRNA Transcriptome in Plants Using Deep Sequencing Data
Next Article in Special Issue
Computer-Aided Approaches for Targeting HIVgp41
Previous Article in Journal / Special Issue
A Comparison of Two Single-Stranded DNA Binding Models by Mutational Analysis of APOBEC3G
Biology 2012, 1(2), 277-296; doi:10.3390/biology1020277

HIV-1 Tat Binding to PCAF Bromodomain: Structural Determinants from Computational Methods

1 Computational Biophysics, German Research School for Simulation Sciences, Computational Biomedicine, Institute for Advanced Simulation (IAS-5), Forschungszentrum Jülich, Jülich D-52425, Germany 2 Institut Pasteur de Montevideo, Mataojo 2020, Montevideo CP 11400, Uruguay 3 Institute for Research in Biomedicine and Barcelona Supercomputing Center Joint Research Program on Computational Biology, Baldiri I Reixac 10, Barcelona S-08028, Spain 4 Jülich Supercomputing Centre, Forschungszentrum Jülich, Jülich D-52425, Germany 5 International Centre for Genetic Engineering and Biotechnology, Trieste 34149, Italy
* Author to whom correspondence should be addressed.
Received: 8 June 2012 / Revised: 9 July 2012 / Accepted: 26 July 2012 / Published: 13 August 2012
(This article belongs to the Special Issue Structural and Molecular Biology of HIV)
View Full-Text   |   Download PDF [873 KB, 20 August 2012; original version 13 August 2012]   |   Browse Figures


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.
Keywords: Tat; PCAF BRD; HIV-1; docking; protein-protein interaction Tat; PCAF BRD; HIV-1; docking; protein-protein interaction
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
MDPI and ACS Style

Quy, V.C.; Pantano, S.; Rossetti, G.; Giacca, M.; Carloni, P. HIV-1 Tat Binding to PCAF Bromodomain: Structural Determinants from Computational Methods. Biology 2012, 1, 277-296.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here


Cited By

[Return to top]
Biology EISSN 2079-7737 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert