Open AccessAmyloid-β peptide (1–42) aggregation induced by copper ions under acidic conditions
Author(s) -
Yannan Bin,
Xia Li,
Yonghui He,
Shu Chen,
Juan Xiang
Publication year - 2013
Publication title -
acta biochimica et biophysica sinica
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.771
H-Index - 57
eISSN - 1745-7270
pISSN - 1672-9145
DOI - 10.1093/abbs/gmt044
Subject(s) - circular dichroism , chemistry , steric effects , fibril , protein aggregation , biophysics , morphology (biology) , amyloid (mycology) , incubation , beta sheet , peptide , fluorescence spectroscopy , copper , amorphous solid , crystallography , fluorescence , biochemistry , stereochemistry , inorganic chemistry , organic chemistry , genetics , physics , quantum mechanics , biology
It is well known that the aggregation of amyloid-β peptide (Aβ) induced by Cu²⁺ is related to incubation time, solution pH, and temperature. In this work, the aggregation of Aβ₁₋₄₂ in the presence of Cu²⁺ under acidic conditions was studied at different incubation time and temperature (e.g. 25 and 37°C). Incubation temperature, pH, and the presence of Cu²⁺ in Aβ solution were confirmed to alter the morphology of aggregation (fibrils or amorphous aggregates), and the morphology is pivotal for Aβ neurotoxicity and Alzheimer disease (AD) development. The results of atomic force microscopy (AFM) indicated that the formation of Aβ fibrous morphology is preferred at lower pH, but Cu²⁺ induced the formation of amorphous aggregates. The aggregation rate of Aβ was increased with the elevation of temperature. These results were further confirmed by fluorescence spectroscopy and circular dichroism spectroscopy and it was found that the formation of β-sheet structure was inhibited by Cu²⁺ binding to Aβ. The result was consistent with AFM observation and the fibrillation process was restrained. We believe that the local charge state in hydrophilic domain of Aβ may play a dominant role in the aggregate morphology due to the strong steric hindrance. This research will be valuable for understanding of Aβ toxicity in AD.