title: Solid-state NMR analysis of the β-strand orientation of the protofibrils of amyloid β-protein.
abstract: Alzheimer's disease (AD) is caused by abnormal deposition (fibrillation) of a 42-residue amyloid β-protein (Aβ42) in the brain. During the process of fibrillation, the Aβ42 takes the form of protofibrils with strong neurotoxicity, and is thus believed to play a crucial role in the pathogenesis of AD. To elucidate the supramolecular structure of the Aβ42 protofibrils, the intermolecular proximity of the Ala-21 residues in the Aβ42 protofibrils was analyzed by (13)C-(13)C rotational resonance experiments in the solid state. Unlike the Aβ42 fibrils, an intermolecular (13)C-(13)C correlation was not found in the Aβ42 protofibrils. This result suggests that the β-strands of the Aβ42 protofibrils are not in an in-register parallel orientation. Aβ42 monomers would assemble to form protofibrils with the β-strand conformation, then transform into fibrils by forming intermolecular parallel β-sheets.
authors.affiliation: Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Doi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Masuda
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Irie
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Akagi
authors.forename: Youko
authors.initials: Y
authors.lastname: Monobe
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Imazawa
authors.forename: K
authors.initials: K
authors.lastname: Takegoshi
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002247:Carbon Isotopes; D006801:Humans; D007553:Isotope Labeling; D046529:Microscopy, Electron, Transmission; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D016229:Amyloid beta-Peptides; D002247:Carbon Isotopes; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)