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Characterization of Mn(II) ion binding to the amyloid-beta peptide in Alzheimer's disease
Stockholm Univ, Dept Biochem & Biophys, Svante Arrhenius Vag 16C, S-10691 Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
Stockholm Univ, Dept Biochem & Biophys, Svante Arrhenius Vag 16C, S-10691 Stockholm, Sweden.;Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc NVS, H1,Novum Pl 5, S-14157 Stockholm, Sweden..
Stockholm Univ, Dept Biochem & Biophys, Svante Arrhenius Vag 16C, S-10691 Stockholm, Sweden.;NICPB, Akad Tee 23, EE-12618 Tallinn, Estonia..
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2016 (English)In: Journal of Trace Elements in Medicine and Biology, ISSN 0946-672X, E-ISSN 1878-3252, Vol. 38, 183-193 p.Article in journal (Refereed) Published
Abstract [en]

Growing evidence links neurodegenerative diseases to metal exposure. Aberrant metal ion concentrations have been noted in Alzheimer's disease (AD) brains, yet the role of metals in AD pathogenesis remains unresolved. A major factor in AD pathogenesis is considered to be aggregation of and amyloid formation by amyloid-beta (A beta) peptides. Previous studies have shown that A beta displays specific binding to Cu(II) and Zn(II) ions, and such binding has been shown to modulate A beta aggregation. Here, we use nuclear magnetic resonance (NMR) spectroscopy to show that Mn(II) ions also bind to the N-terminal part of the A beta(1-40) peptide, with a weak binding affinity in the milli- to micromolar range. Circular dichroism (CD) spectroscopy, solid state atomic force microscopy (AFM), fluorescence spectroscopy, and molecular modeling suggest that the weak binding of Mn(II) to A beta may not have a large effect on the peptide's aggregation into amyloid fibrils. However, identification of an additional metal ion displaying A beta binding reveals more complex AD metal chemistry than has been previously considered in the literature.

Place, publisher, year, edition, pages
2016. Vol. 38, 183-193 p.
Keyword [en]
Manganese, Neurodegeneration, Metal-protein binding, Spectroscopy, Molecular dynamics
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-308063DOI: 10.1016/j.jtemb.2016.03.009ISI: 000385473600023PubMedID: 27085215OAI: oai:DiVA.org:uu-308063DiVA: diva2:1050888
Available from: 2016-11-30 Created: 2016-11-23 Last updated: 2016-11-30Bibliographically approved

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