Conformational characterization of native and L17A/F19A-substituted dutch-typeβ-amyloid peptides

Kai Cyuan He, Yi Ru Chen, Chu Ting Liang, Shi Jie Huang, Chung Ying Tzeng, Chi Fon Chang, Shing Jong Huang, Hsien Bin Huang*, Ta Hsien Lin

*此作品的通信作者

研究成果: Article同行評審

4 引文 斯高帕斯(Scopus)

摘要

Some mutations which occur in the α/β-discordant region (resides 15 to 23) of β-amyloid peptide (Aβ) lead to familial Alzheimer’s disease (FAD). In vitro studies have shown that these genetic mutations could accelerate Aβaggregation. We recently showed that mutations in this region could alter the structural propensity, resulting in a different aggregative propensity of Aβ. Whether these genetic mutations display similar effects remains largely unknown. Here, we characterized the structural propensity and aggregation kinetics of Dutch-type Aβ40 (Aβ40(E22Q)) and its L17A/F19A-substituted mutant (Aβ40(L17A/F19A/E22Q)) using circular dichroism spectroscopy, nuclear magnetic spectroscopy, and thioflavin T fluorescence assay. In comparison with wild-type Aβ40, we found that Dutch-type mutation, unlikeArtic-typemutation(E22G),doesnot reduce theα-helicalpropensity of theα/β-discordant region in sodium dodecyl sulfate micellar solution. Moreover, we found that Aβ40(L17A/F19A/E22Q) displays a higher α-helical propensity of the α/β-discordant region and a slower aggregation rate than Aβ40(E22Q), suggesting that the inhibition of aggregationmight be via increasing the α-helical propensity of the α/β-discordant region, similar to that observed in wild-type and Artic-type Aβ40. Taken together, Dutch-type and Artic-type mutations adopt different mechanisms to promote Aβaggregation, however, the L17A/F19A mutation could increase the α-helical propensities of both Dutch-type and Artic-type Aβ40 and inhibit their aggregation.

原文English
文章編號2571
期刊International Journal Of Molecular Sciences
21
發行號7
DOIs
出版狀態Published - 1 4月 2020

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