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 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 14-3-3sigma at a resolution of 1.28A. 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.
Schumacher
Benjamin
B
Chemical Genomics Centre of the Max-Planck-Society, Dortmund, Germany.
Mondry
Justine
J
Thiel
Philipp
P
Weyand
Michael
M
Ottmann
Christian
C
D048948:14-3-3 Proteins / Q000737:chemistry / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D055503:Protein Multimerization; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism*
D048948:14-3-3 Proteins; D016159:Tumor Suppressor Protein p53