Exploring the interactions of iron and zinc with the microtubule binding repeats R1 and R4

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⁺.