Change search
ReferencesLink to record
Permanent link

Direct link
Influence of Residue 22 on the Folding, Aggregation Profile, and Toxicity of the Alzheimer's Amyloid beta Peptide
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Show others and affiliations
2009 (English)In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 97, no 1, 277-285 p.Article in journal (Refereed) Published
Abstract [en]

Several biophysical techniques have been used to determine differences in the aggregation profile (i.e., the secondary structure, aggregation propensity, dynamics, and morphology of amyloid structures) and the effects on cell viability of three variants of the amyloid beta peptide involved in Alzheimer's disease. We focused our study on the Glu(22) residue, comparing the effects of freshly prepared samples and samples aged for at least 20 days. In the aged samples, a high propensity for aggregation and beta-sheet secondary structure appears when residue 22 is capable of establishing polar (Glu(22) in wild-type) or hydrophobic (Val(22) in E22V) interactions. The Arctic variant (E22G) presents a mixture of mostly disordered and a-helix structures (with low beta-sheet contribution). Analysis of transmission electron micrographs and atomic force microscopy images of the peptide variants after aging showed significant quantitative and qualitative differences in the morphology of the formed aggregates. The effect on human neuroblastoma cells of these A beta(12-28) variants does not correlate with the amount of beta-sheet of the aggregates. In samples allowed to age, the native sequence was found to have an insignificant effect on cell viability, whereas the Arctic variant (E22G), the E22V variant, and the slightly-aggregating control (F19G-F20G) had more prominent effects.

Place, publisher, year, edition, pages
2009. Vol. 97, no 1, 277-285 p.
National Category
URN: urn:nbn:se:su:diva-35415DOI: 10.1016/j.bpj.2009.04.017ISI: 000267871000027PubMedID: 19580765OAI: diva2:287253
Available from: 2010-01-18 Created: 2010-01-18 Last updated: 2012-11-20Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Visa, NeusGräslund, AstridBarth, Andreas
By organisation
Department of Biochemistry and BiophysicsDepartment of Molecular Biology and Functional Genomics
In the same journal
Biophysical Journal

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 87 hits
ReferencesLink to record
Permanent link

Direct link