title: 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.
authors.affiliation: †Department of Chemistry, University at Albany, State University of New York, 1400 Washington Avenue, Albany, New York 12222, United States.
authors.forename: Maruda
authors.initials: M
authors.lastname: Shanmugasundaram
authors.affiliation: †Department of Chemistry, University at Albany, State University of New York, 1400 Washington Avenue, Albany, New York 12222, United States.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Kurouski
authors.affiliation: §Department of Biological Sciences and Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37235, United States.
authors.forename: William
authors.initials: W
authors.lastname: Wan
authors.affiliation: §Department of Biological Sciences and Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37235, United States.
authors.forename: Gerald
authors.initials: G
authors.lastname: Stubbs
authors.affiliation: ⊥BioTools Incorporated, 17546 Bee Line Highway, Jupiter, Florida 33458, United States.
authors.forename: Rina K
authors.initials: RK
authors.lastname: Dukor
authors.affiliation: ⊥BioTools Incorporated, 17546 Bee Line Highway, Jupiter, Florida 33458, United States.|#Department of Chemistry, Syracuse University, 1-014 Center for Science and Technology, Syracuse, New York 13244, United States.
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Nafie
authors.affiliation: †Department of Chemistry, University at Albany, State University of New York, 1400 Washington Avenue, Albany, New York 12222, United States.
authors.forename: Igor K
authors.initials: IK
authors.lastname: Lednev
mesh_terms: D002942:Circular Dichroism; D004926:Escherichia coli; D006863:Hydrogen-Ion Concentration; D018625:Microscopy, Atomic Force; D011328:Prions / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013055:Spectrophotometry, Infrared; D013059:Spectrum Analysis, Raman
chemical_list: D011328:Prions