specific recognition of p53 tetramers by peptides derived from p53 interacting proteinsp53四聚体的特定识别肽来源于p53蛋白相互作用.pdfVIP

Specific Recognition of p53 Tetramers by Peptides Derived from p53 Interacting Proteins 1. 2. 1 1 3 Ronen Gabizon , Tobias Brandt , Shahar Sukenik , Noa Lahav , Mario Lebendiker , 3 2,4,5 1 Deborah E. Shalev , Dmitry Veprintsev *, Assaf Friedler * 1 Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel, 2 MRC Laboratory of Molecular Biology, Cambridge, United Kingdom, 3 The Wolfson Centre for Applied Structural Biology, The Hebrew University of Jerusalem, Jerusalem, Israel, 4 Laboratory of Biomolecular Research, Paul Scherrer Institut, Villigen, Switzerland, 5 Department of Biology, ETH Zurich, Zurich, Switzerland Abstract 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