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

被引：75

作者：

Schumacher, Benjamin ^{[1
]}

Mondry, Justine ^{[1
]}

Thiel, Philipp ^{[1
]}

Weyand, Michael ^{[1
]}

Ottmann, Christian ^{[1
]}

机构：

[1] Max Planck Gesell, Chem Genom Ctr, D-44227 Dortmund, Germany

来源：

FEBS LETTERS | 2010年 / 584卷 / 08期

关键词：

14-3-3; protein; Protein-protein interaction; Stabilizing molecule; p53; regulation; X-ray crystallography; RECOGNITION; BINDING; PHOSPHORYLATION; ASSOCIATION; ACTIVATION; PROTEINS;

D O I：

10.1016/j.febslet.2010.02.065

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1443 / 1448

页数：6

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