title: Molecular structure of amyloid fibrils formed by residues 127 to 147 of the human prion protein.
abstract: Amyloid fibrils are filamentous and insoluble forms of peptides or proteins. Proline has long been considered to be incompatible with the cross-beta structural motif of amyloid fibrils. On the basis of solid-state NMR spectroscopy data, we present a structural model of an in-register parallel beta sheet for the amyloid fibrils formed from a human prion protein fragment, huPrP(127-47). We have developed a simple solid-state NMR spectroscopy technique to identify solvent-protected backbone amide protons in a H/D exchange experiment without disaggregating the amyloid fibrils, from which we find that proline residue P(137) does not disrupt the beta-sheet structure from G(127) to G(142). We suggest that the resultant kink at P(137) generates a twist between adjacent peptide strands to maintain hydrogen bonding in the beta-sheet regions flanking the P(137) residue. Although proline can be well integrated into the cross-beta structure of amyloid fibrils, the kink formed at the position of the proline residue will considerably weaken the hydrogen bonding between the neighboring strands, especially when the mutation site is near the central region of a beta sheet.
authors.affiliation: Department of Chemistry, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei 106, Taiwan.
authors.forename: Ni-Shian
authors.initials: NS
authors.lastname: Lin
authors.forename: John Ching-Hao
authors.initials: JC
authors.lastname: Chao
authors.forename: Hsin-Mei
authors.initials: HM
authors.lastname: Cheng
authors.forename: Fang-Chieh
authors.initials: FC
authors.lastname: Chou
authors.forename: Chi-Fon
authors.initials: CF
authors.lastname: Chang
authors.forename: Yun-Ru
authors.initials: YR
authors.lastname: Chen
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chang
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Huang
authors.forename: Jerry C C
authors.initials: JC
authors.lastname: Chan
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011328:Prions / Q000737:chemistry* / Q000378:metabolism; D011392:Proline / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D011789:Quantum Theory
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011328:Prions; C551486:huPrP(127-47); D011392:Proline