naa a22 4500 528786725 20180924065501.0 cr unu---uuuuu 180924e20120531xx s 000 0 eng 10.3929/ethz-b-000050997 doi 10.1371/journal.pone.0038060 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/50997 Specific Recognition of p53 Tetramers by Peptides Derived from p53 Interacting Proteins [Elektronische Daten] [Ronen Gabizon, Tobias Brandt, Shahar Sukenik, Noa Lahav, Mario Lebendiker, Deborah E. Shalev, Dmitry Veprintsev, Assaf Friedler] PLoS ONE Open access ethresearch Oligomerization plays a major role in regulating the activity of many proteins, and in modulating their interactions. p53 is a homotetrameric transcription factor that has a pivotal role in tumor suppression. Its tetramerization domain is contained within its C-terminal domain, which is a site for numerous protein-protein interactions. Those can either depend on or regulate p53 oligomerization. Here we screened an array of peptides derived from proteins known to bind the tetrameric p53 C-terminal domain (p53CTD) and identified ten binding peptides. We quantitatively characterized their binding to p53CTD using fluorescence anisotropy. The peptides bound tetrameric p53CTD with micromolar affinities. Despite the high charge of the binding peptides, electrostatics contributed only mildly to the interactions. NMR studies indicated that the peptides bound p53CTD at defined sites. The most significant chemical shift deviations were observed for the peptides WS100B(81-92), which bound directly to the p53 tetramerization domain, and PKCα(281-295), which stabilized p53CTD in circular dichroism thermal denaturation studies. Using analytical ultracentrifugation, we found that several of the peptides bound preferentially to p53 tetramers. Our results indicate that the protein-protein interactions of p53 are dependent on the oligomerization state of p53. We conclude that peptides may be used to regulate the oligomerization of p53. Creative Commons Attribution 3.0 Unported http://creativecommons.org/licenses/by/3.0 ethresearch Gabizon Ronen joint author Brandt Tobias joint author Sukenik Shahar joint author Lahav Noa joint author Lebendiker Mario joint author Shalev Deborah E. joint author Veprintsev Dmitry joint author Friedler Assaf joint author PLoS ONE San Francisco, CA, USA : Public Library of Science 7 (5), p. e38060 1932-6203 http://hdl.handle.net/20.500.11850/50997 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/50997 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Gabizon Ronen joint author ETHRESEARCH 700 1- Brandt Tobias joint author ETHRESEARCH 700 1- Sukenik Shahar joint author ETHRESEARCH 700 1- Lahav Noa joint author ETHRESEARCH 700 1- Lebendiker Mario joint author ETHRESEARCH 700 1- Shalev Deborah E. joint author ETHRESEARCH 700 1- Veprintsev Dmitry joint author ETHRESEARCH 700 1- Friedler Assaf joint author ETHRESEARCH 773 0- PLoS ONE San Francisco, CA, USA : Public Library of Science 7 (5), p. e38060 1932-6203 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access