Vibrational Circular Dichroism Reveals Supramolecular Chirality Inversion of α-Synuclein Peptide Assemblies upon Interactions with Anionic Membranes
Abstract
Parkinson's disease is an incurable neurodegenerative disorder caused by the aggregation of α-synuclein (AS). This amyloid protein contains a 12-residue-long segment, AS71-82, that triggers AS pathological aggregation. This peptide is then essential to better understand the polymorphism and the dynamics of formation of AS fibrillar structures. In this work, vibrational circular dichroism showed that AS71-82 is random coil in solution and forms parallel β-sheet fibrillar aggregates in the presence of anionic vesicles. Vibrational circular dichroism, with transmission electronic microscopy, revealed that the fibrillar structures exhibit a nanoscale tape-like morphology with a preferential supramolecular helicity. Whereas the structure handedness of some other amyloid peptides has been shown to be driven by pH, that of AS71-82 is controlled by peptide concentration and peptide-to-lipid (P:L) molar ratio. At low concentrations and low P:L molar ratios, AS71-82 assemblies have a left-twisted handedness, whereas at high concentrations and high P:L ratios, a right-twisted handedness is adopted. Left-twisted assemblies interconvert into right-twisted ones with time, suggesting a maturation of the amyloid structures. As fibril species w...Continue Reading
References
Formation of insulin amyloid fibrils followed by FTIR simultaneously with CD and electron microscopy
Citations
α-Synuclein: An All-Inclusive Trip Around its Structure, Influencing Factors and Applied Techniques.
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