Binding of natively unfolded HIF-1alpha ODD domain to p53.

Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor that plays a crucial role in mediating oxygen response in the cell. Using biophysical techniques, we characterized two fragments of the HIF-1alpha subunit, one the full-length ODD domain (residues 403-603) and the second comprising the N-TAD (N-transactivation domain) and inhibitory domain (residues ...
530-698). Both were unstructured in solution under physiological conditions and so belong to the family of natively unfolded proteins. The HIF-1alpha ODD domain binds weakly to the isolated p53 core domain but tightly to full-length p53 to give a complex of one HIF-1alpha ODD domain with a p53 dimer. By being unstructured, the HIF-1alpha ODD domain can thread both its binding sites through the p53 multimer and bind tightly by the "chelate effect." These results support the idea that hypoxic p53-mediated apoptosis does involve the direct binding of HIF-1alpha to p53.
Mesh Terms:
Apoptosis, Base Sequence, Binding Sites, Circular Dichroism, DNA, DNA-Binding Proteins, Humans, Hypoxia, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, In Vitro Techniques, Kinetics, Multiprotein Complexes, Nuclear Proteins, Osmolar Concentration, Peptide Fragments, Protein Binding, Protein Folding, Protein Structure, Secondary, Protein Structure, Tertiary, Recombinant Proteins, Transcription Factors, Tumor Suppressor Protein p53
Mol. Cell
Date: Jan. 07, 2005
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