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

Article type: Research Article

Authors: Yang, Xiao-Hui^a | Huang, Han-Chang^b | Chen, Lin^a | Xu, Wei^b | Jiang, Zhao-Feng^{b; *}

Affiliations: [a] College of Life Science, Capital Normal University, Beijing, China | [b] College of Arts and Science, Beijing Union University, Beijing, China

Correspondence: [*] Address for correspondence: Prof. Zhao-Feng Jiang, Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, China. Tel.: +86 10 64900138; Fax: +86 10 64900143; E-mail: zhaofeng@buu.edu.cn.

Note: [] Communicated by Ralph Martins

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, 23,6,13,14Aβ1-40.

Keywords: Alzheimer's disease, amyloid-β peptide, β-sheet structure, copper

DOI: 10.3233/JAD-2009-1186

Journal: Journal of Alzheimer's Disease, vol. 18, no. 4, pp. 799-810, 2009