LAUSR

Amyloid fibrillation of α-synuclein is implicated in the pathogenesis of Parkinson’s disease and heavy metal ions such as Fe3+, Zn2+, and Cu2+ are known to be involved in the process. In this work, we explored the use of FTIR spectroscopy to look into the modulation effects of Fe3+, Zn2+, and Cu2+ on the amyloid fibrillation of α-synuclein. We performed a curve-fitting analysis on the FTIR amide I bands of these α-synuclein fibril systems, namely, the pristine fibril and the fibrils prepared in the presence of Fe3+, Zn2+, and Cu2+. We found that the α-synuclein fibrils under the influences of metal ions all possessed a parallel β-sheet structure, turn structure, and disordered structure, similar to that of pristine α-synuclein fibril. We also observed metal-induced increases in the proportions of the β-sheet secondary structure within the α-synuclein fibrils, with Fe3+ being the most effective inducer. We performed second derivative analysis of the side chain carboxylic groups of α-synuclein fibrils and found that the side chain microenvironment of the α-synuclein fibrils was more influenced by Fe3+ than Zn2+, and Cu2+. In addition, our atomic force microscopic study revealed that the morphologies of α-synuclein fibrils under the influence of Fe3+ was quite different from that of the Zn2+ and Cu2+ systems. Our FTIR results suggested that the modulation effects of Fe3+, Zn2+, and Cu2+ on α-synuclein fibrillation occurred at both secondary and quaternary structural levels. At last, we proposed a mechanistic hypothesis to interpret how metal ions could affect the morphology of α-synuclein amyloid fibril based on the conformational plasticity properties of intrinsically disordered proteins.