umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Quenched hydrogen/deuterium exchange NMR characterization of amyloid-β peptide aggregates formed in the presence of Cu2+ or Zn2+
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Show others and affiliations
2009 (English)In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 276, no 15, 4051-4060 p.Article in journal (Refereed) Published
Abstract [en]

Alzheimer's disease, a neurodegenerative disorder causing synaptic impairment and neuronal cell death, is strongly correlated with aggregation of the amyloid-β peptide (Aβ). Divalent metal ions such as Cu2+ and Zn2+ are known to significantly affect the rate of aggregation and morphology of Aβ assemblies in vitro and are also found at elevated levels within cerebral plaques in vivo. The present investigation characterized the architecture of the aggregated forms of Aβ(1–40) and Aβ(1–42) in the presence or absence of either Cu2+ or Zn2+ using quenched hydrogen/deuterium exchange combined with solution NMR spectroscopy. The NMR analyses provide a quantitative and residue-specific structural characterization of metal-induced Aβ aggregates, showing that both the peptide sequence and the type of metal ion exert an impact on the final architecture. Common features among the metal-complexed peptide aggregates are two solvent-protected regions with an intervening minimum centered at Asn27, and a solvent-accessible N-terminal region, Asp1–Lys16. Our results suggest that Aβ in complex with either Cu2+ or Zn2+ can attain an aggregation-prone β-strand–turn–β-strand motif, similar to the motif found in fibrils, but where the metal binding to the N-terminal region guides the peptide into an assembly distinctly different from the fibril form.

Place, publisher, year, edition, pages
Wiley InterScience , 2009. Vol. 276, no 15, 4051-4060 p.
Keyword [en]
Alzheimer's disease, amyloid-β peptide, Cu2+, H/D exchange NMR, Zn2+
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:umu:diva-25819DOI: 10.1111/j.1742-4658.2009.07113.xOAI: oai:DiVA.org:umu-25819DiVA: diva2:234064
Available from: 2009-09-04 Created: 2009-09-04 Last updated: 2017-12-13Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Olofsson, AndersLindhagen Persson, MalinVestling, MonikaSauer-Eriksson, ElisabethÖhman, Anders
By organisation
Department of Medical Biochemistry and BiophysicsDepartment of Chemistry
In the same journal
The FEBS Journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 171 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf