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+. The interaction of Fe2+ and Zn2+ with tau peptide R1 (tau244–274) and R4 (tau337–368), the first and fourth microtubule-binding repeats of tau protein, lead to the metalation with the consequence of conformational changes. [Display omitted] •R1 and R4 are the first and fourth repeats in the microtubule binding domain of tau.•Interaction of Zn2+ and Fe2+ with tau peptides R1 and R4 lead to the complexation.•These interactions lead to the conformational and structural changes of R1 and R4.•There is no such evidence for the complexation of R1 and R4 with Fe3+.•NMR spectroscopy showed that Fe2+ complexes are low spin diamagnetic.