Coordinating to three histidine residues: Cu(II) promotes oligomeric and fibrillar amyloid-beta peptide to precipitate in a non-beta aggregation manner.
Cu(II) has been shown in vitro to profoundly promote the aggregation of amyloid-beta peptide (Abeta), a key pathological event in Alzheimer's disease. We investigated both the effect of Cu(II) on the secondary structure transformation of Abeta and the probable residues involved in the chelation to Cu(II). The effects of Cu(II) on Abeta 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 Abeta 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 Abeta mutant, (23,6,13,14)Abeta(1-40).
Yang
Xiao-Hui
XH
College of Life Science, Capital Normal University, Beijing, China.
Huang
Han-Chang
HC
Chen
Lin
L
Xu
Wei
W
Jiang
Zhao-Feng
ZF
D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000378:metabolism; D011232:Chemical Precipitation; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D005453:Fluorescence; D006639:Histidine / Q000737:chemistry* / Q000187:drug effects; D011485:Protein Binding; D017433:Protein Structure, Secondary / Q000187:drug effects
D016229:Amyloid beta-Peptides; D006639:Histidine; D003300:Copper