Conformational Characterization of Native and L17A/F19A-Substituted Dutch-Type β-Amyloid Peptides
| Autor: | Shing Jong Huang, Chu Ting Liang, Ta Hsien Lin, Chung Ying Tzeng, Kai Cyuan He, Shi Jie Huang, Chi-Fon Chang, Yi Ru Chen, Hsien-Bin Huang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Circular dichroism β-amyloid peptide Mutant E22Q Peptide medicine.disease_cause 01 natural sciences Protein Structure Secondary lcsh:Chemistry chemistry.chemical_compound β amyloid familial Alzheimer’s disease Sodium dodecyl sulfate lcsh:QH301-705.5 Spectroscopy Aβ chemistry.chemical_classification Mutation Sodium Dodecyl Sulfate General Medicine Computer Science Applications CD Dutch-type mutation Thioflavin 010402 general chemistry Catalysis Article Inorganic Chemistry 03 medical and health sciences α/β-discordant Alzheimer Disease medicine Humans Physical and Theoretical Chemistry Molecular Biology Amyloid beta-Peptides FAD Organic Chemistry In vitro Peptide Fragments NMR 0104 chemical sciences 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 chemistry Amino Acid Substitution Biophysics |
| Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 7 International Journal of Molecular Sciences, Vol 21, Iss 2571, p 2571 (2020) |
| ISSN: | 1422-0067 |
| Popis: | Some mutations which occur in the &alpha /&beta discordant region (resides 15 to 23) of &beta amyloid peptide (A&beta ) lead to familial Alzheimer&rsquo s disease (FAD). In vitro studies have shown that these genetic mutations could accelerate A&beta aggregation. We recently showed that mutations in this region could alter the structural propensity, resulting in a different aggregative propensity of A&beta Whether these genetic mutations display similar effects remains largely unknown. Here, we characterized the structural propensity and aggregation kinetics of Dutch-type A&beta 40 (A&beta 40(E22Q)) and its L17A/F19A-substituted mutant (A&beta 40(L17A/F19A/E22Q)) using circular dichroism spectroscopy, nuclear magnetic spectroscopy, and thioflavin T fluorescence assay. In comparison with wild-type A&beta 40, we found that Dutch-type mutation, unlike Artic-type mutation (E22G), does not reduce the &alpha helical propensity of the &alpha discordant region in sodium dodecyl sulfate micellar solution. Moreover, we found that A&beta 40(L17A/F19A/E22Q) displays a higher &alpha discordant region and a slower aggregation rate than A&beta 40(E22Q), suggesting that the inhibition of aggregation might be via increasing the &alpha discordant region, similar to that observed in wild-type and Artic-type A&beta 40. Taken together, Dutch-type and Artic-type mutations adopt different mechanisms to promote A&beta aggregation, however, the L17A/F19A mutation could increase the &alpha helical propensities of both Dutch-type and Artic-type A&beta 40 and inhibit their aggregation. |
| Databáze: | OpenAIRE |
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