title: Polymorphism of amyloid fibrils formed by a peptide from the yeast prion protein Sup35: AFM and Tip-Enhanced Raman Scattering studies.
abstract: Aggregation of prion proteins is the cause of various prion related diseases. The infectious form of prions, amyloid aggregates, exist as multiple strains. The strains are thought to represent structurally different prion protein molecules packed into amyloid aggregates, but the knowledge on the structure of different types of aggregates is limited. Here we report on the use of AFM (Atomic Force Microscopy) and TERS (Tip-Enhanced Raman Scattering) to study morphological heterogeneity and access underlying conformational features of individual amyloid aggregates. Using AFM we identified the morphology of amyloid fibrils formed by the peptide (CGNNQQNY) from the yeast prion protein Sup35 that is critically involved in the aggregation of the full protein. TERS results demonstrate that morphologically different amyloid fibrils are composed of a distinct set of conformations. Fibrils formed at pH 5.6 are composed of a mixture of peptide conformations (β-sheets, random coil and α-helix) while fibrils formed in pH~2 solution primarily have β-sheets. Additionally, peak positions in the amide III region of the TERS spectra suggested that peptides have parallel arrangement of β-sheets for pH~2 fibrils and antiparallel arrangement for fibrils formed at pH 5.6. We also developed a methodology for detailed analysis of the peptide secondary structure by correlating intensity changes of Raman bands in different regions of TERS spectra. Such correlation established that structural composition of peptides is highly localized with large contribution of unordered secondary structures on a fibrillar surface.
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198, United States; Department of Physics, University of Nebraska Omaha, Omaha, NE 68182, United States. Electronic address: akrasnos@unomaha.edu.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Krasnoslobodtsev
authors.affiliation: IPHT-Leibniz Institute of Photonic Technology, Albert-Einstein-Str. 9, D-07745 Jena, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Deckert-Gaudig
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198, United States.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: IPHT-Leibniz Institute of Photonic Technology, Albert-Einstein-Str. 9, D-07745 Jena, Germany; Institute for Physical Chemistry and Abbe Center of Photonics, University of Jena, Helmholtzweg 4, D-07743 Jena, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Deckert
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198, United States. Electronic address: ylyubchenko@unmc.edu.
authors.forename: Yuri L
authors.initials: YL
authors.lastname: Lyubchenko
mesh_terms: D000682:Amyloid / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D000072002:Prion Proteins / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D013059:Spectrum Analysis, Raman
chemical_list: D000682:Amyloid; D010455:Peptides; D000072002:Prion Proteins
keywords: AFM; Aggregation; Amyloid; Prion; TERS