Research Article-Interactions of Iron and Zinc with the Microtubule Binding Repeats R1 and R4 of Tau Protein

Published: 4 May 2020| Version 1 | DOI: 10.17632/ftfkn5zvst.1
Contributors:
Soha Ahmadi, Bing Wu, Ronald Soong, Shaolong Zhu,
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Description

The dyshomeostasis of copper, iron and zinc ions in pathological conditions, which are critically involved in many brain activities, may result in an accumulation of them in the brain that has been reported for the patients with Alzheimer's disease. Conformational change is one of the consequences of metal-peptide interaction as we observed for the interaction of the Cu(II) with microtubule binding repeats of tau protein, which ultimately cause peptide aggregation. Herein, we show that interaction of Zn(II), Fe(II), and Fe(III) with full-length tau peptide R1 (tau244–274) and R4 (tau337–368), the first and fourth microtubule binding repeats of tau protein, lead to the conformational changes. And while the Electrospray ionization-mass spectrometry (ESI-MS) confirmed the complexation of Zn(II) and Fe(II) with both R1 and R4, there is no evidence for metalation of R1 or R4 with Fe(III). References: (1) Ahmadi, S.; Zhu, S.; Sharma, R.; Wu, B.; Soong, R.; Majumdar, R. D.; Wilson, D. J.; Simpson, A. J.; Kraatz, H.-B. Aggregation of Microtubule Binding Repeats of Tau Protein Is Promoted by Cu(II). ACS Omega 2019, 4 (3), 5356–5366. https://doi.org/10.1021/acsomega.8b03595. (2) Ahmadi, S.; Zhu, S.; Sharma, R.; Wilson, D. J.; Kraatz, H.-B. Interaction of Metal Ions with Tau Protein. The Case for a Metal-Mediated Tau Aggregation. J. Inorg. Biochem. 2019, 194, 44–51. (3) Ahmadi, S.; Ebralidze, I. I.; She, Z.; Kraatz, H.-B. Electrochemical Studies of Tau Protein-Iron Interactions—Potential Implications for Alzheimer’s Disease. Electrochim. Acta 2017, 236, 384–393. https://doi.org/10.1016/j.electacta.2017.03.175.

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Institutions

University of Toronto at Scarborough, University of Toronto

Categories

Bioinorganic Chemistry, Zinc, Protein Aggregation, Alzheimer's Disease, Iron, Tau

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