title: Orientation of aromatic residues in amyloid cores: structural insights into prion fiber diversity.
abstract: Structural conversion of one given protein sequence into different amyloid states, resulting in distinct phenotypes, is one of the most intriguing phenomena of protein biology. Despite great efforts the structural origin of prion diversity remains elusive, mainly because amyloids are insoluble yet noncrystalline and therefore not easily amenable to traditional structural-biology methods. We investigate two different phenotypic prion strains, weak and strong, of yeast translation termination factor Sup35 with respect to angular orientation of tyrosines using polarized light spectroscopy. By applying a combination of alignment methods the degree of fiber orientation can be assessed, which allows a relatively accurate determination of the aromatic ring angles. Surprisingly, the strains show identical average orientations of the tyrosines, which are evenly spread through the amyloid core. Small variations between the two strains are related to the local environment of a fraction of tyrosines outside the core, potentially reflecting differences in fibril packing.
authors.affiliation: Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-41296 Gothenburg, Sweden; reymer@chalmers.se norden@chalmers.se.
authors.forename: Anna
authors.initials: A
authors.lastname: Reymer
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142; and Howard Hughes Medical Institute and.
authors.forename: Kendra K
authors.initials: KK
authors.lastname: Frederick
authors.affiliation: Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-41296 Gothenburg, Sweden;
authors.forename: Sandra
authors.initials: S
authors.lastname: Rocha
authors.affiliation: Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-41296 Gothenburg, Sweden;
authors.forename: Tamás
authors.initials: T
authors.lastname: Beke-Somfai
authors.affiliation: Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-41296 Gothenburg, Sweden;
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Kitts
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142; and Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Susan
authors.initials: S
authors.lastname: Lindquist
authors.affiliation: Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-41296 Gothenburg, Sweden; reymer@chalmers.se norden@chalmers.se.
authors.forename: Bengt
authors.initials: B
authors.lastname: Nordén
mesh_terms: D000595:Amino Acid Sequence; D024322:Amino Acids, Aromatic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010454:Peptide Termination Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011328:Prions / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013057:Spectrum Analysis / Q000379:methods; D014443:Tyrosine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D024322:Amino Acids, Aromatic; D000682:Amyloid; D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014443:Tyrosine
keywords: Sup35 strains; linear dichroism; polarized light; prion proteins; tyrosine