Structural and Binding Properties on Aβ Mature Fibrils Due to the Histidine Tautomeric Effect

Many studies have focused on histidine behaviors in misfolding diseases. However, histidine behaviors on mature fibrils are still unknown. In the current study, we investigated mature fibrils with various histidine states to understand the structural properties of the histidine tautomeric effect on mature fibrils. Our results show that substituting chain 1 with different histidine states affects Aβ structural properties in A2, D7-G9, H14-Q15, S26-N27, and G33-G37 regions. The binding free energies with substituted fibrils were influenced not only along the axial direction, but also between duplex fibrils. Our results suggest that substituted (ϵδδ) preferentially disturbed the stability among the current mature fibrils. Further, H-bonded network differences indicate that twisted morphologies in mature fibrils are derived from the position and orientation of the imidazole ring in histidines. Our current study helps to elucidate histidine behaviors on mature fibrils, which will present opportunities to understand the misfolding mechanisms.