title: Mapping the core of the beta(2)-microglobulin amyloid fibril by H/D exchange.
abstract: Despite numerous efforts, the lack of detailed structural information on amyloid fibrils has hindered clarification of the mechanism of their formation. Here, we describe a novel procedure for characterizing the conformational flexibility of beta(2)-microglobulin amyloid fibrils at single-residue resolution that uses H/D exchange of amide protons combined with NMR analysis. The results indicate that most residues in the middle region of the molecule, including the loop regions in the native structure, form a rigid beta-sheet core, whereas the the N- and C-termini are excluded from this core. The extensively hydrogen-bonded beta-sheet core explains the remarkable rigidity and stability of amyloid fibrils. The present method could be used to obtain residue-specific conformational information of various amyloid fibrils, even though it does not provide a high resolution three-dimensional structure.
authors.affiliation: Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Hoshino
authors.forename: Hidenori
authors.initials: H
authors.lastname: Katou
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Hagihara
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Hironobu
authors.initials: H
authors.lastname: Naiki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Goto
mesh_terms: D000686:Amyloidosis / Q000378:metabolism*; D002942:Circular Dichroism; D003903:Deuterium / Q000378:metabolism; D004121:Dimethyl Sulfoxide; D006801:Humans; D006859:Hydrogen / Q000378:metabolism*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D001613:beta 2-Microglobulin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D001613:beta 2-Microglobulin; D006859:Hydrogen; D003903:Deuterium; D004121:Dimethyl Sulfoxide