https://scholars.lib.ntu.edu.tw/handle/123456789/625955
標題: | Site specific NMR characterization of abeta-40 oligomers cross seeded by abeta-42 oligomers | 作者: | Chang, Han-Wen Ma, Ho-I Wu, Yi-Shan Lee, Ming-Che Chung-Yueh Yuan, Eric Huang, Shing-Jong Cheng, Yu-Sheng Wu, Meng-Hsin Tu, Ling-Hsien CHUN-CHUNG CHAN |
關鍵字: | AMYLOID-BETA-PROTEIN; ATOMIC-RESOLUTION STRUCTURE; ALZHEIMERS-DISEASE; REVERSE MICELLES; FIBRIL FORMATION; STRUCTURAL BASIS; A-BETA-42; AGGREGATION; PEPTIDE; STATE | 公開日期: | 29-七月-2022 | 出版社: | ROYAL SOC CHEMISTRY | 卷: | 13 | 期: | 29 | 起(迄)頁: | 8526 | 來源出版物: | Chemical science | 摘要: | Extracellular accumulation of β amyloid peptides of 40 (Aβ40) and 42 residues (Aβ42) has been considered as one of the hallmarks in the pathology of Alzheimer's disease. In this work, we are able to prepare oligomeric aggregates of Aβ with uniform size and monomorphic structure. Our experimental design is to incubate Aβ peptides in reverse micelles (RMs) so that the peptides could aggregate only through a single nucleation process and the size of the oligomers is confined by the physical dimension of the reverse micelles. The hence obtained Aβ oligomers (AβOs) are 23 nm in diameter and they belong to the category of high molecular-weight (MW) oligomers. The solid-state NMR data revealed that Aβ40Os adopt the structural motif of β-loop-β but the chemical shifts manifested that they may be structurally different from low-MW AβOs and mature fibrils. From the thioflavin-T results, we found that high-MW Aβ42Os can accelerate the fibrillization of Aβ40 monomers. Our protocol allows performing cross-seeding experiments among oligomeric species. By comparing the chemical shifts of Aβ40Os cross seeded by Aβ42Os and those of Aβ40Os prepared in the absence of Aβ42Os, we observed that the chemical states of E11, K16, and E22 were altered, whereas the backbone conformation of the β-sheet region near the C-terminus was structurally invariant. The use of reverse micelles allows hitherto the most detailed characterization of the structural variability of Aβ40Os. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/625955 | ISSN: | 2041-6520 | DOI: | 10.1039/d2sc01555b |
顯示於: | 化學系 |
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