Effect of Copper and Zinc on the Single Molecule Self-Affinity of Alzheimer's Amyloid-β Peptides

TitleEffect of Copper and Zinc on the Single Molecule Self-Affinity of Alzheimer's Amyloid-β Peptides
Publication TypeJournal Article
Year of Publication2016
AuthorsHane, F. T., R. Hayes, B. Y. Lee, and Z. Leonenko
JournalPLoS ONE
Volume11
Start Pagee0147488
Issue1
Paginatione0147488
Date Published01/2016
Abstract

The presence of trace concentrations of metallic ions, such as copper and zinc, has previously been shown to drastically increase the aggregation rate and neurotoxicity of amyloid-β (Aβ), the peptide implicated in Alzheimer’s disease (AD). The mechanism of why copper and zinc accelerate Aβ aggregation is poorly understood. In this work, we use single molecule force spectroscopy (SMFS) to probe the kinetic and thermodynamic parameters (dissociation constant, Kd, kinetic dissociation rate, koff, and free energy, ΔG) of the dissociation of an Aβ dimer, the amyloid species which initiates the amyloid cascade. Our results show that nanomolar concentrations of copper do not change the single molecule affinity of Aβ to another Aβ peptide in a statistically significant way, while nanomolar concentrations of zinc decrease the affinity of Aβ-Aβ by an order of magnitude. This suggests that the binding of zinc ion to Aβ may interfere with the binding of Aβ-Aβ, leading to a lower self-affinity.

URLhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147488
DOI10.1371/journal.pone.0147488
Refereed DesignationRefereed
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