title: Structural characterization of polyglutamine fibrils by solid-state NMR spectroscopy.
abstract: Protein aggregation via polyglutamine stretches occurs in a number of severe neurodegenerative diseases such as Huntington's disease. We have investigated fibrillar aggregates of polyglutamine peptides below, at, and above the toxicity limit of around 37 glutamine residues using solid-state NMR and electron microscopy. Experimental data are consistent with a dry fibril core of at least 70-80 Å in width for all constructs. Solid-state NMR dipolar correlation experiments reveal a largely β-strand character of all samples and point to tight interdigitation of hydrogen-bonded glutamine side chains from different sheets. Two approximately equally frequent populations of glutamine residues with distinct sets of chemical shifts are found, consistent with local backbone dihedral angles compensating for β-strand twist or with two distinct sets of side-chain conformations. Peptides comprising 15 glutamine residues are present as single extended β-strands. Data obtained for longer constructs are most compatible with a superpleated arrangement with individual molecules contributing β-strands to more than one sheet and an antiparallel assembly of strands within β-sheets.
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Schneider
authors.forename: Miria C
authors.initials: MC
authors.lastname: Schumacher
authors.forename: Henrik
authors.initials: H
authors.lastname: Mueller
authors.forename: Deepak
authors.initials: D
authors.lastname: Nand
authors.forename: Volker
authors.initials: V
authors.lastname: Klaukien
authors.forename: Henrike
authors.initials: H
authors.lastname: Heise
authors.forename: Dietmar
authors.initials: D
authors.lastname: Riedel
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wolf
authors.forename: Elmar
authors.initials: E
authors.lastname: Behrmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Raunser
authors.forename: Ralf
authors.initials: R
authors.lastname: Seidel
authors.forename: Martin
authors.initials: M
authors.lastname: Engelhard
authors.forename: Marc
authors.initials: M
authors.lastname: Baldus
mesh_terms: D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008854:Microscopy, Electron; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D010455:Peptides; C097188:polyglutamine