Abstract
Amyloid β (Aβ) oligomers are the most neurotoxic forms of Aβ, and Aβ(1-42) is the prevalent Aβ peptide found in the amyloid plaques of Alzheimer's disease patients. Aβ(25-35) is the shortest peptide that retains the toxicity of Aβ(1-42). Aβ oligomers bind to calmodulin (CaM) and calbindin-D28k with dissociation constants in the nanomolar Aβ(1-42) concentration range. Aβ and histidine-rich proteins have a high affinity for transition metal ions Cu(2+), Fe(3+) and Zn(2+). In this work, we show that the fluorescence of Aβ(1-42) HiLyte(TM)-Fluor555 can be used to monitor hexa-histidine peptide (His(6)) interaction with Aβ(1-42). The formation of His(6)/Aβ(1-42) complexes is also supported by docking results yielded by the MDockPeP Server. Also, we found that micromolar concentrations of His(6) block the increase in the fluorescence of Aβ(1-42) HiLyte(TM)-Fluor555 produced by its interaction with the proteins CaM and calbindin-D28k. In addition, we found that the His(6)-tag provides a high-affinity site for the binding of Aβ(1-42) and Aβ(25-35) peptides to the human recombinant cytochrome b(5) reductase, and sensitizes this enzyme to inhibition by these peptides. In conclusion, our results suggest that a His(6)-tag could provide a valuable new tool to experimentally direct the action of neurotoxic Aβ peptides toward selected cellular targets.