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The solvent protection of alzheimer amyloid-beta-(1-42) fibrils as determined by solution NMR spectroscopy.
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine). (Sauer-Eriksson)
Umeå University, Faculty of Science and Technology, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Science and Technology).
Umeå University, Faculty of Science and Technology, Department of Chemistry.
2006 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, Vol. 281, no 1, 477-83 p.Article in journal (Refereed) Published
Description
Abstract [en]

Alzheimer disease is a neurodegenerative disorder that is tightly linked to the self-assembly and amyloid formation of the 39-43-residue-long amyloid-beta (Abeta) peptide. Considerable evidence suggests a correlation between Alzheimer disease development and the longer variants of the peptide, Abeta-(1-42/43). Currently, a molecular understanding for this behavior is lacking. In the present study, we have investigated the hydrogen/deuterium exchange of Abeta-(1-42) fibrils under physiological conditions, using solution NMR spectroscopy. The obtained residue-specific and quantitative map of the solvent protection within the Abeta-(1-42) fibril shows that there are two protected core regions, Glu11-Gly25 and Lys28-Ala42, and that the residues in between, Ser26 and Asn27, as well as those in the N terminus, Asp1-Tyr10, are solvent-accessible. This result reveals considerable discrepancies when compared with a previous investigation on Abeta-(1-40) fibrils and suggests that the additional residues in Abeta-(1-42), Ile41 and Ala42, significantly increase the solvent protection and stability of the C-terminal region Lys28-Ala42. Consequently, our findings provide a molecular explanation for the increased amyloidogenicity and toxicity of Abeta-(1-42) compared with shorter Abeta variants found in vivo.

Place, publisher, year, edition, pages
2006. Vol. 281, no 1, 477-83 p.
Keyword [en]
Amyloid/*chemistry, Amyloid beta-Protein/*chemistry, Deuterium Exchange Measurement, Humans, Microscopy; Atomic Force, Nuclear Magnetic Resonance; Biomolecular, Peptide Fragments/*chemistry, Solubility, Solvents
Identifiers
URN: urn:nbn:se:umu:diva-13607DOI: doi:10.1074/jbc.M508962200PubMedID: 16215229OAI: oai:DiVA.org:umu-13607DiVA: diva2:153278
Available from: 2008-04-08 Created: 2008-04-08 Last updated: 2016-10-25Bibliographically approved

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Olofsson, AndersSauer-Eriksson, ElisabethÖhman, Anders
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Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine)Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Science and Technology)Department of Chemistry

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