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
J. Mol. Biol.
Date: Oct. 03, 2003
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