title: Effect of Copper and Zinc on the Single Molecule Self-Affinity of Alzheimer's Amyloid-β Peptides.
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.
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, Ontario, N2L 3G1, Canada.
authors.forename: Francis T
authors.initials: FT
authors.lastname: Hane
authors.affiliation: Department of Physics and Astronomy, University of Waterloo, Waterloo, Ontario, N2L 3G1, Canada.
authors.forename: Reid
authors.initials: R
authors.lastname: Hayes
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, Ontario, N2L 3G1, Canada.
authors.forename: Brenda Y
authors.initials: BY
authors.lastname: Lee
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, Ontario, N2L 3G1, Canada.|Department of Physics and Astronomy, University of Waterloo, Waterloo, Ontario, N2L 3G1, Canada.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Leonenko
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D008962:Models, Theoretical; D011485:Protein Binding; D015032:Zinc / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D003300:Copper; D015032:Zinc
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