Using peptides to study the interaction between the p53 tetramerization domain and HIV-1 Tat

Biopolymers
Ronen GabizonAssaf Friedler

Abstract

Peptides are valuable tools for studying protein-protein interactions, especially in cases of isolated protein domains and natively unfolded proteins. Here, we used peptides to quantitatively characterize the interaction between the natively unfolded HIV-1 Tat protein and the tetramerization domain of the cellular tumor suppressor protein p53. We used peptide mapping, fluorescence anisotropy, and NMR spectroscopy to perform a detailed structural and biophysical characterization of the interaction between the two proteins and elucidate its molecular mechanism, which have so far been studied using cell-based methods. We show that the p53 tetramerization domain, p53(326-355), binds directly to residues 1-35 and 47-57 in Tat. We have characterized the interaction between p53(326-355) and Tat(47-57) in detail. The p53 residues that are mainly involved in binding to Tat(47-57) are E343 and E349, which bind to the positively charged arginine-rich motif of Tat by a partly electrostatic mechanism. All oligomerization states of p53(326-355) bind Tat(47-57) without inhibiting p53 tetramerization, since the residues in p53(326-355) that bind Tat(47-57) face away from the tetramerization interface. We conclude that p53 is able to bind Tat a...Continue Reading

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Citations

May 7, 2014·The Journal of Physical Chemistry. B·Marganit Cohen-AvrahamiNissim Garti
Jan 15, 2016·AIDS Research and Human Retroviruses·Sergey Iordanskiy, Fatah Kashanchi
Jun 13, 2015·Future Medicinal Chemistry·Koushik ChandraAssaf Friedler
May 3, 2014·Frontiers in Chemistry·Ronen Gabizon, Assaf Friedler
Jun 23, 2016·ChemMedChem·Koushik ChandraAssaf Friedler
Feb 19, 2019·Chemical Science·Anat Iosub-AmirRachel Nechushtai
Mar 18, 2020·Chemistry : a European Journal·Guy MayerAssaf Friedler
Aug 12, 2021·Journal of Virology·Yann BretonMichel J Tremblay

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