Structure of the p53 C-terminus bound to 14-3-3: Implications for stabilization of the p53 tetramer

The adaptor protein 14-3-3 binds to and stabilizes the tumor suppressor p53 and enhances its antitumour activity. In the regulatory C-terminal domain of p53 several 14-3-3 binding motifs have been identified. Here, we report the crystal structure of the extreme C-terminus ( residues 385-393, p53pT387) of p53 in complex with 14-3-3 sigma at a resolution of 1.28 angstrom. p53pT387 is accommodated by 14-3-3 in a yet unrecognized fashion implying a rationale for 14-3-3 binding to the active p53 tetramer. The structure exhibits a potential binding site for small molecules that could stabilize the p53/14-3-3 protein complex suggesting the possibility for therapeutic intervention. Structured summary: MINT-7711943: 14-3-3 sigma (uniprotkb: P31947) and p53 ( uniprotkb: P04637) bind (MI: 0407) by X-ray crystallography ( MI: 0114) MINT-7711931: 14-3-3 sigma ( uniprotkb: P31947) and p53 ( uniprotkb: P04637) bind ( MI: 0407) by isothermal titration calorimetry ( MI: 0065) (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.