title: Amyloid of the prion domain of Sup35p has an in-register parallel beta-sheet structure.
abstract: The [PSI(+)] prion of Saccharomyces cerevisiae is a self-propagating amyloid form of Sup35p, a subunit of the translation termination factor. Using solid-state NMR we have examined the structure of amyloid fibrils formed in vitro from purified recombinant Sup35(1-253), consisting of the glutamine- and asparagine-rich N-terminal 123-residue prion domain (N) and the adjacent 130-residue highly charged M domain. Measurements of magnetic dipole-dipole couplings among (13)C nuclei in a series of Sup35NM fibril samples, (13)C-labeled at backbone carbonyl sites of Tyr, Leu, or Phe residues or at side-chain methyl sites of Ala residues, indicate intermolecular (13)C-(13)C distances of approximately 0.5 nm for nearly all sites in the N domain. Certain sites in the M domain also exhibit intermolecular distances of approximately 0.5 nm. These results indicate that an in-register parallel beta-sheet structure underlies the [PSI(+)] prion phenomenon.
authors.affiliation: Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Shewmaker
authors.forename: Reed B
authors.initials: RB
authors.lastname: Wickner
authors.forename: Robert
authors.initials: R
authors.lastname: Tycko
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D002247:Carbon Isotopes; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010454:Peptide Termination Factors; D011328:Prions / Q000737:chemistry* / Q000648:ultrastructure; D017433:Protein Structure, Secondary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D000682:Amyloid; D002247:Carbon Isotopes; D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins