The N-terminal domain of p53 is natively unfolded.
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:
Apoptosis, Biophysical Phenomena, Biophysics, Cell Division, Chromatography, Gel, Circular Dichroism, Humans, Magnetic Resonance Spectroscopy, Nuclear Proteins, Plasmids, Protein Binding, Protein Folding, Protein Structure, Quaternary, Protein Structure, Secondary, Protein Structure, Tertiary, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Spectrometry, Fluorescence, Tumor Suppressor Protein p53, Ultracentrifugation, Water
Apoptosis, Biophysical Phenomena, Biophysics, Cell Division, Chromatography, Gel, Circular Dichroism, Humans, Magnetic Resonance Spectroscopy, Nuclear Proteins, Plasmids, Protein Binding, Protein Folding, Protein Structure, Quaternary, Protein Structure, Secondary, Protein Structure, Tertiary, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Spectrometry, Fluorescence, Tumor Suppressor Protein p53, Ultracentrifugation, Water
J. Mol. Biol.
Date: Oct. 03, 2003
PubMed ID: 14499615
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