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Charge dependent retardation of amyloid β aggregation by hydrophilic proteins
Lund University.
Lund University.
Lund University.
Lund University.
2014 (English)In: ACS Chemical Neuroscience, E-ISSN 1948-7193, Vol. 5, no 4, p. 266-74Article in journal (Refereed) Published
Abstract [en]

The aggregation of amyloid β peptides (Aβ) into amyloid fibrils is implicated in the pathology of Alzheimer's disease. In light of the increasing number of proteins reported to retard Aβ fibril formation, we investigated the influence of small hydrophilic model proteins of different charge on Aβ aggregation kinetics and their interaction with Aβ. We followed the amyloid fibril formation of Aβ40 and Aβ42 using thioflavin T fluorescence in the presence of six charge variants of calbindin D9k and single-chain monellin. The formation of fibrils was verified with transmission electron microscopy. We observe retardation of the aggregation process from proteins with net charge +8, +2, -2, and -4, whereas no effect is observed for proteins with net charge of -6 and -8. The single-chain monellin mutant with the highest net charge, scMN+8, has the largest retarding effect on the amyloid fibril formation process, which is noticeably delayed at as low as a 0.01:1 scMN+8 to Aβ40 molar ratio. scMN+8 is also the mutant with the fastest association to Aβ40 as detected by surface plasmon resonance, although all retarding variants of calbindin D9k and single-chain monellin bind to Aβ40.

Place, publisher, year, edition, pages
2014. Vol. 5, no 4, p. 266-74
National Category
Physical Chemistry
Identifiers
URN: urn:nbn:se:hkr:diva-18583DOI: 10.1021/cn400124rPubMedID: 24475785OAI: oai:DiVA.org:hkr-18583DiVA, id: diva2:1241314
Available from: 2018-08-23 Created: 2018-08-23 Last updated: 2023-08-28Bibliographically approved

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Cabaleiro-Lago, Celia
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