Influence of Residue 22 on the Folding, Aggregation Profile, and Toxicity of the Alzheimer's Amyloid β Peptide
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 β peptide involved in Alzheimer...
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ftpubmed:oai:pubmedcentral.nih.gov:2711388 2023-05-15T14:57:49+02:00 Influence of Residue 22 on the Folding, Aggregation Profile, and Toxicity of the Alzheimer's Amyloid β Peptide Perálvarez-Marín, Alex Mateos, Laura Zhang, Ce Singh, Shalini Cedazo-Mínguez, Ángel Visa, Neus Morozova-Roche, Ludmilla Gräslund, Astrid Barth, Andreas 2009-07-08 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711388 http://www.ncbi.nlm.nih.gov/pubmed/19580765 https://doi.org/10.1016/j.bpj.2009.04.017 en eng The Biophysical Society http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711388 http://www.ncbi.nlm.nih.gov/pubmed/19580765 http://dx.doi.org/10.1016/j.bpj.2009.04.017 © 2009 by the Biophysical Society. This document may be redistributed and reused, subject to certain conditions (http://www.elsevier.com/wps/find/authorsview.authors/supplementalterms1.0) . Protein Text 2009 ftpubmed https://doi.org/10.1016/j.bpj.2009.04.017 2013-09-02T14:47:30Z 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 β peptide involved in Alzheimer's disease. We focused our study on the Glu22 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 β-sheet secondary structure appears when residue 22 is capable of establishing polar (Glu22 in wild-type) or hydrophobic (Val22 in E22V) interactions. The Arctic variant (E22G) presents a mixture of mostly disordered and α-helix structures (with low β-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 Aβ12–28 variants does not correlate with the amount of β-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. Text Arctic PubMed Central (PMC) Arctic Biophysical Journal 97 1 277 285 |
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Protein Perálvarez-Marín, Alex Mateos, Laura Zhang, Ce Singh, Shalini Cedazo-Mínguez, Ángel Visa, Neus Morozova-Roche, Ludmilla Gräslund, Astrid Barth, Andreas Influence of Residue 22 on the Folding, Aggregation Profile, and Toxicity of the Alzheimer's Amyloid β Peptide |
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Protein |
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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 β peptide involved in Alzheimer's disease. We focused our study on the Glu22 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 β-sheet secondary structure appears when residue 22 is capable of establishing polar (Glu22 in wild-type) or hydrophobic (Val22 in E22V) interactions. The Arctic variant (E22G) presents a mixture of mostly disordered and α-helix structures (with low β-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 Aβ12–28 variants does not correlate with the amount of β-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. |
format |
Text |
author |
Perálvarez-Marín, Alex Mateos, Laura Zhang, Ce Singh, Shalini Cedazo-Mínguez, Ángel Visa, Neus Morozova-Roche, Ludmilla Gräslund, Astrid Barth, Andreas |
author_facet |
Perálvarez-Marín, Alex Mateos, Laura Zhang, Ce Singh, Shalini Cedazo-Mínguez, Ángel Visa, Neus Morozova-Roche, Ludmilla Gräslund, Astrid Barth, Andreas |
author_sort |
Perálvarez-Marín, Alex |
title |
Influence of Residue 22 on the Folding, Aggregation Profile, and Toxicity of the Alzheimer's Amyloid β Peptide |
title_short |
Influence of Residue 22 on the Folding, Aggregation Profile, and Toxicity of the Alzheimer's Amyloid β Peptide |
title_full |
Influence of Residue 22 on the Folding, Aggregation Profile, and Toxicity of the Alzheimer's Amyloid β Peptide |
title_fullStr |
Influence of Residue 22 on the Folding, Aggregation Profile, and Toxicity of the Alzheimer's Amyloid β Peptide |
title_full_unstemmed |
Influence of Residue 22 on the Folding, Aggregation Profile, and Toxicity of the Alzheimer's Amyloid β Peptide |
title_sort |
influence of residue 22 on the folding, aggregation profile, and toxicity of the alzheimer's amyloid β peptide |
publisher |
The Biophysical Society |
publishDate |
2009 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711388 http://www.ncbi.nlm.nih.gov/pubmed/19580765 https://doi.org/10.1016/j.bpj.2009.04.017 |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711388 http://www.ncbi.nlm.nih.gov/pubmed/19580765 http://dx.doi.org/10.1016/j.bpj.2009.04.017 |
op_rights |
© 2009 by the Biophysical Society. This document may be redistributed and reused, subject to certain conditions (http://www.elsevier.com/wps/find/authorsview.authors/supplementalterms1.0) . |
op_doi |
https://doi.org/10.1016/j.bpj.2009.04.017 |
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Biophysical Journal |
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97 |
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1 |
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277 |
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285 |
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