Evaluation of ferritin and transferrin binding to tau protein

Tau protein is a neurodegeneration biomarker. Due to the high concentration of metal ions in the brain, the metallation of tau proteins and their catalytic role in reactive oxygen formation have been identified as a major biochemical pathway of neurodegeneration. High levels of iron ions have been detected in Alzheimer's disease brains. One of biological sources of iron ions are iron-rich proteins, such as transferrin or ferritin. However, the interactions between tau and these metallo-proteins have not been fully characterized. Here, the interactions between the longest form of full-length tau protein (tau441) with iron-rich proteins were detected using electrochemical impedance spectroscopy. Tau441 was immobilized on Au surface, via N-terminal (N-tau-Au film) or Cys-residues (Cys-tau-Au film), and the charge-transfer resistance, R_ct, was monitored prior and post ferritin or transferrin binding. Significant increase in R_ct was observed post transferrin binding above 50μgmL^-1, but not ferritin regardless of concentration with N-tau-Au film. Additionally, the electrochemical trend was linear with respect to transferrin concentration. Electrochemical data indicated low binding by ferritin to N-tau-Au or Cys-tau-Au films. The interaction of apotransferrin or apoferritin with tau films was also evaluated. Electrochemical data may be pointing to the differences in protein binding modes by transferrin compared to ferritin as well as to importance of metal ions in protein-protein interactions.