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An Electron Spin Resonance Analysis of Metal Histidine Coordination In Amyloid-beta

In this work Electron Spin Resonance (ESR) spectroscopy is used to gain more insight into less explored aspects of Cu(II) coordination in amyloid-beta (Aβ). Of the two known Cu(II) coordination modes component I and component II, Zn(II) substitutes Cu(II) from component I only as shown by our CW-ESR results. To obtain molecular level details about changes in component I in the presence of Zn(II), ESEEM experiments are carried out on systematically 15N labeled Aβ peptides. In the presence of one equivalent of Zn(II) approximately half of the peptides use His 14 as an equatorial ligand. Zn(II) also completely displaces Cu(II) from His 6-His 13 simultaneous coordination, while the percentage of Cu(II) coordination to His 13-His 14 dyad is increased. A controversy has existed about the number of histidine residues coordinated to Cu(II) in component II. At excess amounts of Zn(II) ions, component II becomes the dominant Cu(II) coordination mode. In brain tissues affected with Alzheimer's disease the concentration of Zn(II) higher than Cu(II). Hence, it is critical to understand molecular level details of component II. Our results suggest that Cu(II) is coordinated to a single histidine in component II. Furthermore, the His 13 and His 14 were favored as equatorial ligands compared to His 6. Shedding light into the molecular level details of the sub-component metal ion coordination will be critical in understanding the role of metal ions in Alzheimer's disease, as these sub-components may have different functions.


veronika.szalai [at] (Veronika Szalai), 301-975-3792

K. Ishara Silva

University of Pittsburgh, Department of Chemistry

Created August 4, 2014, Updated October 2, 2018