Structural Characterization of Polyglutamine Fibrils by Solid-State NMR Spectroscopy

JOURNAL OF MOLECULAR BIOLOGY

卷:412

Article

Schneider, Robert²  Schumacher, Miria C.¹  Mueller, Henrik²  Nand, Deepak³  Klaukien, Volker²  Heise, Henrike²  Riedel, Dietmar²  Wolf, Gerhard²  Behrmann, Elmar¹  Raunser, Stefan¹  Seidel, Ralf¹  Engelhard, Martin¹  Baldus, Marc³ 

[1] Max Planck Inst Mol Physiol, D-44227 Dortmund, Germany

[2] Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany

[3] Univ Utrecht, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht, Netherlands

关键词: amyloid fibrils;    Huntington's disease;    aggregation;    polyglutamine;    solid-state NMR;   

DOI  :  10.1016/j.jmb.2011.06.045

来源: Elsevier

【 摘 要 】

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 angstrom in width for all constructs. Solid-state NMR dipolar correlation experiments reveal a largely beta-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 beta-strand twist or with two distinct sets of side-chain conformations. Peptides comprising 15 glutamine residues are present as single extended beta-strands. Data obtained for longer constructs are most compatible with a superpleated arrangement with individual molecules contributing beta-strands to more than one sheet and an antiparallel assembly of strands within beta-sheets. (C) 2011 Elsevier Ltd. All rights reserved.

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