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Mariusz Mital Nina E. Wezynfeld Tomasz Frczyk Magdalena Z. Wiloch Urszula E. Wawrzyniak Arkadiusz Bonna Carolin Tumpach Kevin J. Barnham Cathryn L. Haigh Wojciech Bal Simon C. Drew 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2015,127(36):10606-10610
Accumulation of the β‐amyloid (Aβ) peptide in extracellular senile plaques rich in copper and zinc is a defining pathological feature of Alzheimer′s disease (AD). The Aβ1–x (x=16/28/40/42) peptides have been the primary focus of CuII binding studies for more than 15 years; however, the N‐truncated Aβ4–42 peptide is a major Aβ isoform detected in both healthy and diseased brains, and it contains a novel N‐terminal FRH sequence. Proteins with His at the third position are known to bind CuII avidly, with conditional log K values at pH 7.4 in the range of 11.0–14.6, which is much higher than that determined for Aβ1–x peptides. By using Aβ4–16 as a model, it was demonstrated that its FRH sequence stoichiometrically binds CuII with a conditional Kd value of 3×10−14 M at pH 7.4, and that both Aβ4–16 and Aβ4–42 possess negligible redox activity. Combined with the predominance of Aβ4–42 in the brain, our results suggest a physiological role for this isoform in metal homeostasis within the central nervous system. 相似文献