Coordinating to three histidine residues: Cu(II) promotes oligomeric and fibrillar amyloid-β peptide to precipitate in a non-β aggregation manner

Cu(II) has been shown in vitro to profoundly promote the aggregation of amyloid-beta peptide (A beta), a key pathological event in Alzheimer's disease. We investigated both the effect of Cu(II) on the secondary structure transformation of A beta and the probable residues involved in the chelation to Cu(II). The effects of Cu(II) on A beta 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 beta-sheet structure, convert beta-sheeted aggregates into non-beta-sheeted aggregates and promote oligomeric A beta to precipitate in a non-beta-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 A beta mutant, (23,6,13,14)A beta(1-40).