Rapid Filament Supramolecular Chirality Reversal of HET-s (218–289) Prion Fibrils Driven by pH Elevation

Abstract

Amyloid fibril polymorphism is not well understood despite its potential importance for biological activity and associated toxicity. Controlling the polymorphism of mature fibrils including their morphology and supramolecular chirality by postfibrillation changes in the local environment is the subject of this study. Specifically, the effect of pH on the stability and dynamics of HET-s (218-289) prion fibrils has been determined through the use of vibrational circular dichroism (VCD), deep UV resonance Raman, and fluorescence spectroscopies. It was found that a change in solution pH causes deprotonation of Asp and Glu amino acid residues on the surface of HET-s (218-289) prion fibrils and triggers rapid transformation of one supramolecular chiral polymorph into another. This process involves changes in higher order arrangements like lateral filament and fibril association and their supramolecular chirality, while the fibril cross-β core remains intact. This work suggests a hypothetical mechanism for HET-s (218-289) prion fibril refolding and proposes that the interconversion between fibril polymorphs driven by the solution environment change is a general property of amyloid fibrils.

Helical Inversion of Gel Fibrils by Elongation of Perfluoroalkyl Chains as Studied by Vibrational Circular Dichroism

“…The VCD spectrum covers the infrared and near-infrared regions of the circular dichroism spectrum. [17][18][19][20][21] A large number of bands due to the normal modes are utilized to analyze the molecular vibrations of a given molecule in order to determine its detailed conformation. Another advantage of the method is that even a molecule with no electronic absorption in the UV-visible region can be a target.…”

Recent Trends in Chiroptical Spectroscopy: Theory and Applications of Vibrational Circular Dichroism and Raman Optical Activity

“…Empirically, five VCD signature bands in the amide I (C=O stretching, ∼1650 cm −1 ) and amide II (CN stretching, ∼1530 cm −1 ) regions were ascribed to amyloid fibril aggregation, but VCD patterns of different signs and shapes were found for various proteins and peptides . Even for the same protein, a slight variation in fibril preparation may significantly affect their morphology and VCD …”

Dynamic Modulation of Supramolecular Chirality Driven by Factors from Internal to External Levels

“…Beyond the intramolecular and intermolecular factors, there are also various external stimuli that can modulate supramolecular chirality, such as heat, pH, light, sonication, and solvents, and provide abundant references for dynamic tuning . Feringa et al.…”

“…Beyondt he intramolecular and intermolecular factors, there are also various external stimuli that can modulate supramolecular chirality,s uch as heat, [30] pH, [31] light, [32] sonication, [33] and solvents, [34] and provide abundant references for dynamic tuning. [35] Feringa et al reported reversible chirality control by using UV and visible light in as elf-assembling molecular system based on ad ithienylethene photochromic unit functionalized with (R)-1-phenylethylamine-derived amides, in which molecular and supramolecular chirality could communicate.…”