The electrostatic surface of MDM2 modulates the specificity of its interaction with phosphorylated and unphosphorylated p53 peptides

Christopher John Brown; Deepa Srinivasan; Lee Hui Jun; David Coomber; Chandra S Verma; David P Lane

doi:10.4161/cc.7.5.5488

The electrostatic surface of MDM2 modulates the specificity of its interaction with phosphorylated and unphosphorylated p53 peptides

Cell Cycle. 2008 Mar 1;7(5):608-10. doi: 10.4161/cc.7.5.5488. Epub 2007 Dec 26.

Authors

Christopher John Brown¹, Deepa Srinivasan, Lee Hui Jun, David Coomber, Chandra S Verma, David P Lane

Affiliation

¹ Laboratory of Cell Cycle Control, Institute of Molecular and Cell Biology, Singapore.

PMID: 18256546
DOI: 10.4161/cc.7.5.5488

Abstract

Florescence anisotropy measurements using FAM-labelled p53 peptides showed that the binding of the peptides to MDM2 was dependant upon the phosphorylation of p53 at Thr18 and that this binding was modulated by the electrostatic properties of MDM2. In agreement with computational predictions, the binding to phosphorylated p53 peptide, in comparison to the unphosphorylated p53 peptide, was enhanced upon mutation of 3 key residues on the MDM2 surface.

MeSH terms

Crystallography, X-Ray
Fluorescence Polarization
Models, Molecular
Mutation / genetics
Phosphopeptides / metabolism*
Phosphorylation
Protein Binding
Proto-Oncogene Proteins c-mdm2 / chemistry*
Proto-Oncogene Proteins c-mdm2 / metabolism*
Static Electricity
Structure-Activity Relationship
Tumor Suppressor Protein p53 / chemistry*
Tumor Suppressor Protein p53 / metabolism*

Substances

Phosphopeptides
Tumor Suppressor Protein p53
Proto-Oncogene Proteins c-mdm2