Παρασκευή 21 Ιουλίου 2017

IJMS, Vol. 18, Pages 1585: Investigating the Influence of Magnesium Ions on p53–DNA Binding Using Atomic Force Microscopy

IJMS, Vol. 18, Pages 1585: Investigating the Influence of Magnesium Ions on p53–DNA Binding Using Atomic Force Microscopy

International Journal of Molecular Sciences doi: 10.3390/ijms18071585

Authors: Yang Chen Tianyong Gao Yanwei Wang Guangcan Yang

p53 is a tumor suppressor protein that plays a significant role in apoptosis and senescence, preserving genomic stability, and preventing oncogene expression. Metal ions, such as magnesium and zinc ions, have important influences on p53–DNA interactions for stabilizing the structure of the protein and enhancing its affinity to DNA. In the present study, we systematically investigated the interaction of full length human protein p53 with DNA in metal ion solution by atomic force microscopy (AFM). The p53–DNA complexes at various p53 concentrations were scanned by AFM and their images are used to measure the dissociation constant of p53–DNA binding by a statistical method. We found that the dissociation constant of p53 binding DNA is 328.02 nmol/L in physiological buffer conditions. The influence of magnesium ions on p53–DNA binding was studied by AFM at various ion strengths through visualization. We found that magnesium ions significantly stimulate the binding of the protein to DNA in a sequence-independent manner, different from that stimulated by zinc. Furthermore, the high concentrations of magnesium ions can promote p53 aggregation and even lead to the formation of self-assembly networks of DNA and p53 proteins. We propose an aggregation and self-assembly model based on the present observation and discuss its biological meaning.



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