Coordinating to Three Histidine Residues: Cu(II) Promotes Oligomeric and Fibrillar Amyloid-β Peptide to Precipitate in a Non-β Aggregation Manner

Abstract

Cu(II) has been shown in vitro to profoundly promote the aggregation of amyloid-β peptide (Aβ, a key pathological event in Alzheimer's disease. We investigated both the effect of Cu(II) on the secondary structure transformation of Aβ and the probable residues involved in the chelation to Cu(II). The effects of Cu(II) on Aβ was analyzed by the circular dichroism spectra, Th-T fluorescence and sedimentation assay, and the results indicated that Cu(II) could disrupt the already formed β-sheet structure, convert β-sheeted aggregates into non-β-sheeted aggregates and promote oligomeric Aβ to precipitate in a non-β-sheeted aggregation way. Additionally, we confirmed that the function of Cu(II) discussed above was achieved through its interaction with His6, His13, and His14 by investigating an Aβ mutant, ^23,6,13,14Aβ_1-40.