title: Parallel beta-sheets and polar zippers in amyloid fibrils formed by residues 10-39 of the yeast prion protein Ure2p.
abstract: We report the results of solid-state nuclear magnetic resonance (NMR) and atomic force microscopy measurements on amyloid fibrils formed by residues 10-39 of the yeast prion protein Ure2p (Ure2p(10)(-)(39)). Measurements of intermolecular (13)C-(13)C nuclear magnetic dipole-dipole couplings indicate that Ure2p(10)(-)(39) fibrils contain in-register parallel beta-sheets. Measurements of intermolecular (15)N-(13)C dipole-dipole couplings, using a new solid-state NMR technique called DSQ-REDOR, are consistent with hydrogen bonds between side chain amide groups of Gln18 residues. Such side chain hydrogen bonding interactions have been called "polar zippers" by M. F. Perutz and have been proposed to stabilize amyloid fibrils formed by peptides with glutamine- and asparagine-rich sequences, such as Ure2p(10)(-)(39). We propose that polar zipper interactions account for the in-register parallel beta-sheet structure in Ure2p(10)(-)(39) fibrils and that similar peptides will also exhibit parallel beta-sheet structures in amyloid fibrils. We present molecular models for Ure2p(10)(-)(39) fibrils that are consistent with available experimental data. Finally, we show that solid-state (13)C NMR chemical shifts for (13)C-labeled Ure2p(10)(-)(39) fibrils are insensitive to hydration level, indicating that the fibril structure is not affected by the presence or absence of bulk water.
authors.affiliation: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA.
authors.forename: Jerry C C
authors.initials: JC
authors.lastname: Chan
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Oyler
authors.forename: Wai-Ming
authors.initials: WM
authors.lastname: Yau
authors.forename: Robert
authors.initials: R
authors.lastname: Tycko
mesh_terms: D000409:Alanine / Q000737:chemistry; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D002247:Carbon Isotopes; D005973:Glutamine / Q000737:chemistry; D005979:Glutathione Peroxidase; D005998:Glycine / Q000737:chemistry; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000648:ultrastructure; D010649:Phenylalanine / Q000737:chemistry; D011328:Prions / Q000737:chemistry* / Q000648:ultrastructure; D017433:Protein Structure, Secondary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000648:ultrastructure; D014867:Water / Q000737:chemistry
chemical_list: D000682:Amyloid; D002247:Carbon Isotopes; D010446:Peptide Fragments; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins; D014867:Water; D005973:Glutamine; D010649:Phenylalanine; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae; D000409:Alanine; D005998:Glycine