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

Schumacher, Benjamin; Mondry, Justine; Thiel, Philipp; Weyand, Michael; Ottmann, Christian

doi:10.1016/j.febslet.2010.02.065

« Previous Next »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

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.