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

Edited by Hans Eklund

Received 25 November 2009; received in revised form 23 February 2010; accepted 24 February 2010. published online 03 March 2010.

Abstract

The adaptor protein 14-3-3 binds to and stabilizes the tumor suppressor p53 and enhances its anti-tumour 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 14-3-3σ at a resolution of 1.28Å. 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)

Keywords: 14-3-3 protein, Protein–protein interaction, Stabilizing molecule, p53 regulation, X-ray crystallography

a Chemical Genomics Centre of the Max-Planck-Society, Otto-Hahn-Strasse 15, 44227 Dortmund, Germany

Corresponding author. Fax: +49 (0) 231 9742 6479.

1 These authors contributed equally to this work.

PII: S0014-5793(10)00169-9

doi:10.1016/j.febslet.2010.02.065

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