In vitro coordination of Fe-protoheme with amyloid β is non-specific and exhibits multiple equilibria

Abstract

In addition to copper and zinc, heme is thought to play a role in Alzheimer's disease and its metabolism is strongly affected during the course of this disease. Amyloid β, the peptide associated with Alzheimer's disease, was shown to bind heme in vitro with potential catalytic activity linked to oxidative stress. To date, there is no direct determination of the structure of this complex. In this work, we studied the binding mode of heme to amyloid β in different conditions of pH and redox state by using isotopically labelled peptide in combination with advanced magnetic and vibrational spectroscopic methods. Our results show that the interaction between heme and amyloid β leads to a variety of species in equilibrium. The formation of these species seems to depend on many factors suggesting that the binding site is neither very strong nor highly specific. In addition, our data do not support the currently accepted model where a water molecule is bound to the ferric heme as sixth ligand. They also exclude structural models mimicking a peroxidatic site in the amyloid β-Fe-protoheme complexes.