Misfolding of certain proteins and peptides leads to aggregation and toxicity. A neuronal protein, tau, undergoes post-translational modification prior to aggregation [1]. Due to high levels of metal ions in the brain, the metallation of misfolding peptides/proteins plays a critical part in aggregation as well as in the oxidative stress, via formation of the reactive oxygen species (ROS) [2]. We have evaluated coordination of Cu(II) and iron-rich proteins, ferittin, transferrin and heme, to tau441 and its R1-R4 repeat fragments by electrochemical methods. The aggregation of metallo-tau was evaluated by fluorescence spectroscopy and transmission electron microscopy. The coordination of phosphotau and its aggregation were also investigated. The catalytic ability of metallo-tau to generate hydrogen peroxide, and participate in the oxidation/reduction reactions with other biological agents, such as ascorbic acid, was evaluated. The role of phosphorylation and aggregation, or combination thereof on catalytic activity was also tested. The catalytic activity of metallo-phosphotau was dependent on the peptide sequence, phosphosite and nature of metal ion. [1] Wingarten, M. D., Lockwood, A. H., Hwo, S. Y., Kirschner, M. W. Proc. Natl. Acad. Sci. U. S. A. 1975, 72, 1858-1862. [2] Jiang, D., Men, L., Wang, J., Zhang, Y., Chickenyen, S., Wang, Y., Zhou, F. Biochemistry, 2007, 46, 9270-9282; b) Jiang, D., Li, X, Liu, L., Yagnik, G. B., Zhou, F. J. Phys. Chem. 2010, 114, 4896-4903.

Metallation of misfolding tau peptides/protein: Aggregation, phosphorylation and catalytic activity

251st National Meeting (2016)

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