The electrostatic surface of MDM2 modulates the specificity of its interaction with phosphorylated and unphosphorylated p53 peptides.
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.
Brown
Christopher John
CJ
Laboratory of Cell Cycle Control, Institute of Molecular and Cell Biology, Singapore.
Srinivasan
Deepa
D
Jun
Lee Hui
LH
Coomber
David
D
Verma
Chandra S
CS
Lane
David P
DP
D018360:Crystallography, X-Ray; D005454:Fluorescence Polarization; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D010748:Phosphopeptides / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry* / Q000378:metabolism*; D055672:Static Electricity; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism*
D010748:Phosphopeptides; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2