Characterization of Mn(II) ion binding to the amyloid-beta peptide in Alzheimer's disease
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
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.
Manganese, Neurodegeneration, Metal-protein binding, Spectroscopy, Molecular dynamics
Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:uu:diva-308063DOI: 10.1016/j.jtemb.2016.03.009ISI: 000385473600023PubMedID: 27085215OAI: oai:DiVA.org:uu-308063DiVA: diva2:1050888