title: Solid-state NMR reveals a close structural relationship between amyloid-β protofibrils and oligomers.
abstract: We have studied tertiary contacts in protofibrils and mature fibrils of amyloid-β (Aβ) peptides using solid-state NMR spectroscopy. Although intraresidue contacts between Glu-22 and Ile-31 were found in Aβ protofibrils, these contacts were completely absent in mature Aβ fibrils. This is consistent with the current models of mature Aβ fibrils. As these intramolecular contacts have also been reported in Aβ oligomers, our measurements suggest that Aβ protofibrils are structurally more closely related to oligomers than to mature fibrils. This suggests that some structural alterations have to take place on the pathway from Aβ oligomers/protofibrils to mature fibrils, in agreement with a model that suggests a conversion of intramolecular hydrogen-bonded structures of Aβ oligomers to the intermolecular stabilized mature fibrils (Hoyer, W., Grönwall, C., Jonsson, A., Ståhl, S., and Härd, T. (2008) Proc. Natl. Acad. Sci. U.S.A. 105, 5099-5104).
authors.affiliation: Institute of Medical Physics and Biophysics, University of Leipzig, D-04107 Leipzig, Germany.
authors.forename: Holger A
authors.initials: HA
authors.lastname: Scheidt
authors.forename: Isabel
authors.initials: I
authors.lastname: Morgado
authors.forename: Daniel
authors.initials: D
authors.lastname: Huster
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D018698:Glutamic Acid / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D007532:Isoleucine / Q000737:chemistry; D008956:Models, Chemical; D016874:Neurofibrillary Tangles / Q000737:chemistry* / Q000473:pathology; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D016229:Amyloid beta-Peptides; D007532:Isoleucine; D018698:Glutamic Acid