title: An infrared spectroscopy approach to follow β-sheet formation in peptide amyloid assemblies.
abstract: Amyloidogenic peptides and proteins play a crucial role in a variety of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. These proteins undergo a spontaneous transition from a soluble, often partially folded form, into insoluble amyloid fibrils that are rich in β-sheets. Increasing evidence suggests that highly dynamic, polydisperse folding intermediates, which occur during fibril formation, are the toxic species in the amyloid-related diseases. Traditional condensed-phase methods are of limited use for characterizing these states because they typically only provide ensemble averages rather than information about individual oligomers. Here we report the first direct secondary-structure analysis of individual amyloid intermediates using a combination of ion mobility spectrometry-mass spectrometry and gas-phase infrared spectroscopy. Our data reveal that oligomers of the fibril-forming peptide segments VEALYL and YVEALL, which consist of 4-9 peptide strands, can contain a significant amount of β-sheet. In addition, our data show that the more-extended variants of each oligomer generally exhibit increased β-sheet content.
authors.affiliation: Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, Berlin 14195, Germany.
authors.forename: Jongcheol
authors.identifier: 0000-0001-5844-4585
authors.initials: J
authors.lastname: Seo
authors.affiliation: Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, Berlin 14195, Germany.|Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany.
authors.forename: Waldemar
authors.identifier: 0000-0001-6757-3151
authors.initials: W
authors.lastname: Hoffmann
authors.affiliation: Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, Berlin 14195, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Warnke
authors.affiliation: Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, Berlin 14195, Germany.
authors.forename: Xing
authors.initials: X
authors.lastname: Huang
authors.affiliation: Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, Berlin 14195, Germany.
authors.forename: Sandy
authors.initials: S
authors.lastname: Gewinner
authors.affiliation: Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, Berlin 14195, Germany.
authors.forename: Wieland
authors.identifier: 0000-0003-0564-203X
authors.initials: W
authors.lastname: Schöllkopf
authors.affiliation: Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, California 93106, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bowers
authors.affiliation: Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, Berlin 14195, Germany.
authors.forename: Gert
authors.initials: G
authors.lastname: von Helden
authors.affiliation: Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, Berlin 14195, Germany.|Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany.
authors.forename: Kevin
authors.initials: K
authors.lastname: Pagel
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure; D013058:Mass Spectrometry; D046529:Microscopy, Electron, Transmission; D009842:Oligopeptides / Q000737:chemistry*; D000072757:Protein Conformation, beta-Strand; D017510:Protein Folding; D013055:Spectrophotometry, Infrared / Q000379:methods*
chemical_list: D016229:Amyloid beta-Peptides; D009842:Oligopeptides