English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Structural characterization of polyglutamine fibrils by solid-state NMR spectroscopy

Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Schneider, R., Schumacher, M. C., Müeller, H., Nand, D., Klaukien, V., Heise, H., et al. (2011). Structural characterization of polyglutamine fibrils by solid-state NMR spectroscopy. Journal of molecular biology, 412(1), 121-136. doi:10.1016/j.jmb.2011.06.045.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0028-63DE-6
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 A 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.