Spectrometric Studies on Interaction Between Metal Ions and DNA-Binding Domain of Tumor Suppressor Protein p53

Site-specific recognition and DNA-binding activity of tumor suppressor protein p53 are crucial for its tumor suppressor function. Previous reports have shown that metal ions could affect specific recognition and DNA-binding activity of p53 DNA-binding domain (p53DBD). In this study, we investigated the binding reaction between p53DBD and nine kinds of metal ions by fluorescence titration method, the binding affinity of metal ions to p53DBD is Fe3+ > Zn2+ > Cu2+ > Ca2+ > Mg2+ > Ba2+ > Mn2+ > Ni2+ > Co2+. Analysis of the far-UV CD data suggested that the binding of Ba2+, Ca2+, Co2+, Mn2+ and Ni2+ did not induce changes in protein secondary structure. The binding of Zn2+, Mg2+ and Fe3+ induced a subtle conformational change, whereas the binding of Cu2+ resulted in a lot of loss in its helical content. Analysis of 8-anilino-1-naphthalenesulfonic acid binding data showed that the binding of Mg2+ enhanced hydrophobic exposure on protein surface such as Zn2+, whereas Fe3+ decreased hydrophobic exposure. Therefore, Mg2+ and Fe3+ may be one of potential factors to affect or regulate the transactivation of p53.