Exploring the interactions of iron and zinc with the microtubule binding repeats R1 and R4
Soha Ahmadi, Bing Wu, Ronald Song, Shaolong Zhu, Andre Simpson, Derek J. Wilson, Heinz-Bernhard Kraatz
Journal of Inorganic Biochemistry
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 Cu2+ with microtubule binding repeats of tau protein, which ultimately cause peptide aggregation. Herein, we show that interaction of Zn2+, Fe2+, and Fe3+ 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 Zn2+ and Fe2+ with both R1 and R4, there is no evidence for metalation of R1 or R4 with Fe3+.
Circular dichroism, Secondary structure, Ligand binding, Tertiary structure, Biochemistry, Inorganic chemistry