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