%0 Journal Article
%A Schneider, R.
%A Schumacher, M.C.
%A Mueller, H.
%A Nand, D.
%A Klaukien, V.
%A Heise, H.
%A Riedel, D.
%A Wolf, G.
%A Behrmann, E.
%A Raunser, S.
%A Seidel, R.
%A Engelhard, M.
%A Baldus, M.
%T Structural Characterization of Polyglutamine Fibrils by Solid-State NMR Spectroscopy
%J Journal of molecular biology
%V 412
%@ 0022-2836
%C Amsterdam [u.a.]
%I Elsevier
%M PreJuSER-16612
%P 121 - 136
%D 2011
%Z This work was supported by the Deutsche Forschungsgemeinschaft (Grant RA 1781/1-1), the Max Planck Society, the Fonds der chemischen Industrie (Grant 684052), and Netherlands Organisation for Scientific Research (Grant 700.26.121). R.S. thanks the Deutsche Forschungsgemeinschaft graduate school 782 "Spectroscopy and Dynamics of Molecular Coils and Aggregates" for a PhD fellowship.
%X 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.
%K Magnetic Resonance Spectroscopy: methods
%K Microscopy, Electron
%K Peptides: chemical synthesis
%K Peptides: chemistry
%K Peptides (NLM Chemicals)
%K polyglutamine (NLM Chemicals)
%K J (WoSType)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:21763317
%U <Go to ISI:>//WOS:000294523300012
%R 10.1016/j.jmb.2011.06.045
%U https://juser.fz-juelich.de/record/16612