FEBS Letters
Volume 584, Issue 8 , Pages 1443-1448, 16 April 2010

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

Edited by Hans Eklund

  • Benjamin Schumacher

      Affiliations

    • Chemical Genomics Centre of the Max-Planck-Society, Otto-Hahn-Strasse 15, 44227 Dortmund, Germany
    • These authors contributed equally to this work.
  • ,
  • Justine Mondry

      Affiliations

    • Chemical Genomics Centre of the Max-Planck-Society, Otto-Hahn-Strasse 15, 44227 Dortmund, Germany
    • These authors contributed equally to this work.
  • ,
  • Philipp Thiel

      Affiliations

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

      Affiliations

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

      Affiliations

    • Chemical Genomics Centre of the Max-Planck-Society, Otto-Hahn-Strasse 15, 44227 Dortmund, Germany
    • Corresponding Author InformationCorresponding author. Fax: +49 (0) 231 9742 6479.

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

To access this article, please choose from the options below

Login to an existing account or Register a new account.

  • Purchase this article for 31.50 USD (You must login/register to purchase this article)

    Online access for 24 hours. The PDF version can be downloaded as your permanent record.

  • Subscribe to this title

    Get unlimited online access to this article and all other articles in this title 24/7 for one year.

  • Claim access now

    For current subscribers with Society Membership or Account Number.

  • Visit SciVerse ScienceDirect to see if you have access via your institution.
 

PII: S0014-5793(10)00169-9

doi:10.1016/j.febslet.2010.02.065

FEBS Letters
Volume 584, Issue 8 , Pages 1443-1448, 16 April 2010