title: The N-terminal domain of p53 is natively unfolded.
abstract: p53 is one of the key molecules regulating cell proliferation, apoptosis and tumor suppression by integrating a wide variety of signals. The structural basis for this function is still poorly understood. p53 appears to exercise its function as a modular protein in which different functions are associated with distinct domains. Presumably, p53 contains both folded and partially structured parts. Here, we have investigated the structure of the isolated N-terminal part of p53 (amino acid residues 1-93) using biophysical techniques. We demonstrate that this domain is devoid of tertiary structure and largely missing secondary structure elements. It exhibits a large hydrodynamic radius, typical for unfolded proteins. These findings suggest strongly that the entire N-terminal part of p53 is natively unfolded under physiological conditions. Furthermore, the binding affinity to its functional antagonist Mdm2 was investigated. A comparison of the binding of human Mdm2 to the N-terminal part of p53 and full-length p53 suggests that unfolded and folded parts of p53 function synergistically.
mesh_terms: D017209:Apoptosis; D055592:Biophysical Phenomena; D001703:Biophysics; D002455:Cell Division; D002850:Chromatography, Gel; D002942:Circular Dichroism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009687:Nuclear Proteins; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry; D051736:Proto-Oncogene Proteins c-mdm2; D013050:Spectrometry, Fluorescence; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry*; D014461:Ultracentrifugation; D014867:Water / Q000737:chemistry
chemical_list: D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D014867:Water; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2