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A method of predicting the in vitro fibril formation propensity of Aβ40 mutants based on their inclusion body levels in E. coli
Lund University.
Germany.
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2019 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, no 1Article in journal (Refereed) Published
Abstract [en]

Overexpression of recombinant proteins in bacteria may lead to their aggregation and deposition in inclusion bodies. Since the conformational properties of proteins in inclusion bodies exhibit many of the characteristics typical of amyloid fibrils. Based on these findings, we hypothesize that the rate at which proteins form amyloid fibrils may be predicted from their propensity to form inclusion bodies. To establish a method based on this concept, we first measured by SDS-PAGE and confocal microscopy the level of inclusion bodies in E. coli cells overexpressing the 40-residue amyloid-beta peptide, Aβ40, wild-type and 24 charge mutants. We then compared these results with a number of existing computational aggregation propensity predictors as well as the rates of aggregation measured in vitro for selected mutants. Our results show a strong correlation between the level of inclusion body formation and aggregation propensity, thus demonstrating the power of this approach and its value in identifying factors modulating aggregation kinetics.

Place, publisher, year, edition, pages
2019. Vol. 9, no 1
National Category
Physical Chemistry
Identifiers
URN: urn:nbn:se:hkr:diva-19158DOI: 10.1038/s41598-019-39216-zISI: 000460391500063PubMedID: 30842594OAI: oai:DiVA.org:hkr-19158DiVA, id: diva2:1296199
Available from: 2019-03-14 Created: 2019-03-14 Last updated: 2022-09-15Bibliographically approved

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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
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  • Other locale
More languages
Output format
  • html
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