Binding of Rad51 and other peptide sequences to a promiscuous, highly electrostatic binding site in p53.
Homologous recombination is repressed by the binding of p53 to Rad51. We identified by fluorescence and NMR spectroscopy that peptides corresponding to residues 179-190 of Rad51 bind to the core domain of p53 in a site that overlaps with its specific DNA binding site. The p53 site is quite promiscuous, since it also binds peptides derived from 53BP1, 53BP2, Hif-1alpha, and BCL-X(L) in overlapping regions. Binding is mediated mainly by a strong, nonspecific, electrostatic component and is fine tuned by specific interactions. Competition of the different proteins with each other and with specific DNA for a single site in p53 could be a factor in regulation of its activity.
Friedler
Assaf
A
Cambridge Centre for Protein Engineering, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom.
Veprintsev
Dmitry B
DB
Rutherford
Trevor
T
von Glos
Karoly I
KI
Fersht
Alan R
AR
D016880:Anisotropy; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry; D007477:Ions; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009154:Mutation; D010455:Peptides / Q000737:chemistry; D010750:Phosphoproteins / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051135:Rad51 Recombinase; D011995:Recombination, Genetic; D013050:Spectrometry, Fluorescence; D055672:Static Electricity; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism; D000071857:Tumor Suppressor p53-Binding Protein 1; D014461:Ultracentrifugation
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007477:Ions; D010455:Peptides; D010750:Phosphoproteins; C498301:TP53BP1 protein, human; C090468:TP53BP2 protein, human; D016159:Tumor Suppressor Protein p53; D000071857:Tumor Suppressor p53-Binding Protein 1; D004247:DNA; C495153:RAD51 protein, human; D051135:Rad51 Recombinase