This title appears in the Scientific Report :
2012
Please use the identifier:
http://hdl.handle.net/2128/4900 in citations.
Please use the identifier: http://hdl.handle.net/2128/8842 in citations.
Please use the identifier: http://dx.doi.org/10.3390/biology1020277 in citations.
HIV-1 Tat Binding to PCAF Bromodomain: Structural Determinants from Computational Methods
HIV-1 Tat Binding to PCAF Bromodomain: Structural Determinants from Computational Methods
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. Acet...
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Personal Name(s): | Quy, Vo Cam (Corresponding author) |
---|---|
Pantano, Sergio / Giacca, Mauro / Rossetti, Giulia / Carloni, Paolo (Corresponding Author) | |
Contributing Institute: |
Jülich Supercomputing Center; JSC Computational Biomedicine; IAS-5 GRS; GRS |
Published in: | Biology, 1 (2012) 2, S. 277 - 296 |
Imprint: |
Basel
MDPI
2012
|
DOI: |
10.3390/biology1020277 |
PubMed ID: |
24832227 |
Document Type: |
Journal Article |
Research Program: |
Computational Science and Mathematical Methods |
Link: |
OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://hdl.handle.net/2128/8842 in citations.
Please use the identifier: http://dx.doi.org/10.3390/biology1020277 in citations.
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. |