title: Structural variations in the cross-beta core of amyloid beta fibrils revealed by deep UV resonance Raman spectroscopy.
abstract: Understanding fibrillogenesis at a molecular level requires detailed structural characterization of amyloid fibrils. The combination of deep UV resonance Raman (DUVRR) spectroscopy and post mortem hydrogen-deuterium exchange (HX) was utilized for probing parallel vs antiparallel beta-sheets in fibrils prepared from full-length Abeta(1-40) and Abeta(34-42) peptides, respectively. Using previously published structural data based on solid-state NMR analysis, we verified the applicability of Asher's approach for the quantitative characterization of peptide conformation in the Abeta(1-40) fibril core. We found that the conformation of the parallel beta-sheet in the Abeta(1-40) fibril core is atypical for globular proteins, while in contrast, the antiparallel beta-sheet in Abeta(32-42) fibrils is a common structure in globular proteins. In contrast to the case for globular proteins, the conformations of parallel and antiparallel beta-sheets in Abeta fibril cores are substantially different, and their differences can be distinguished by DUVRR spectroscopy.
authors.affiliation: Department of Chemistry University at Albany, SUNY, 1400 Washington Avenue, Albany, New York 12222, USA.
authors.forename: Ludmila A
authors.initials: LA
authors.lastname: Popova
authors.forename: Ravindra
authors.initials: R
authors.lastname: Kodali
authors.forename: Ronald
authors.initials: R
authors.lastname: Wetzel
authors.forename: Igor K
authors.initials: IK
authors.lastname: Lednev
mesh_terms: D000577:Amides / Q000737:chemistry; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D041961:Deuterium Exchange Measurement; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D013059:Spectrum Analysis, Raman; D014466:Ultraviolet Rays
chemical_list: D000577:Amides; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)