Zinc Metal Ion Affected the Structural Stability of Amyloid-Like Nanofibrils

Zahraa S. Al-Garawi


Synthetic peptides that self-assemble into well-defined structures with a cross-β arrangement are called amyloid-like fibrils. Amyloids are associated with a list of disorders and neuro-degenerative diseases, such as Alzheimer's and Parkinson`s disease. We previously showed that amyloid-like nanofibrils with a repeating motif “IHIH” were functional fibrils. They were able to bind a metal ion through imidazole moieties and mimic the native carbonic anhydrase enzyme by hydrolysing the CO2 molecule. Thus, these synthetic amyloid fibrils were suggest-ed to be good candidates to moderate and update the modern enzymatic molecules. This study aims to shed a light on the stability of these amyloid nanofibrils over a study period of 25 days, in the presence/absence of a metal ion. The work continued for approximately 7 months in the Biochemistry department, School of Life Sciences at the University of Sussex in the United Kingdom. A set of designed peptides with a repeating motif “IHIH” were ex-plored, based on some structural studies. Short and long peptides with free ends as well as closed ends were investigated. Peptides allowed to self-assemble with and without a metal ion (zinc) were then examined using circular dichroism, fluorimetry and electron microscopy for structural biophysical analysis. Regardless of the metal ion contribution, peptides showed stable secondary structures with a -sheet conformation for the incubation time of 25 days. Their morphologies did not appear to change over time. However, the presence of a zinc ion has an effect on the secondary structure of the mature fibrils. Results indicated that fibrils grown with the zinc ion have a significantly higher propensity to form -sheets secondary structures during incubation time. The presence of a zinc ion also affected the dimensions of the amyloid-like fibrils by the end of the study course, at which point they significantly re-duced. This effect of zinc ion on synthetic amyloid fibrils has not been previously reported. The stabilities of the zinc-nanofibrils point to their potential for use in modifying or updating the enzyme-mimic analytical reactions. The effect of adding zinc on the fibrillation seems to be crucial. Although it apparently improved the -sheet assembly, it affected the width/length of the synthetic amyloids. This effect could be promising toward reducing the generation of amyloid fibrils and ultimately understanding the pathogenesis of Alzheimer disease.


Functional fibrils, amyloids, structural stability, circular dichroism.

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DOI: http://dx.doi.org/10.23851/mjs.v29i3.622


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