Copper (II) modulates in vitro aggregation of a tau peptide.
Copper (II) has been implicated in the pathology of Alzheimer's disease (AD) for the impaired homeostatic mechanism found in the brains of AD patients. Here we studied the binding properties of Cu(II) with the first microtubule-binding repeat, encompassing residues 256-273 of the human tau441 sequence. Additionally, the effect of Cu(II) on the assembly of this repeat was also investigated. Our results indicate that Cu(II) can bind to this repeat with His(268) involved and has an inhibiting effect on the in vitro aggregation of this repeat. This work provides new insight into the role of Cu(II) in Alzheimer's disease.
Zhou
Lian-Xiu
LX
Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, PR China.
Du
Jin-Tang
JT
Zeng
Zhi-Yang
ZY
Wu
Wei-Hui
WH
Zhao
Yu-Fen
YF
Kanazawa
Kenji
K
Ishizuka
Yasuko
Y
Nemoto
Tadashi
T
Nakanishi
Hiroshi
H
Li
Yan-Mei
YM
D000544:Alzheimer Disease / Q000378:metabolism; D002942:Circular Dichroism; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology; D006639:Histidine / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
D010446:Peptide Fragments; D016875:tau Proteins; D006639:Histidine; D003300:Copper