1. Clusterin inhibits Aß42 aggregation through a "strawberry model" as detected by FRET-FCS.
- Author
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Lingwan Xu, Shijun Tian, Xianglei Peng, Ying Hua, Wenxuan Yang, Longwei Chen, Shilei Liu, Wenzheng Wu, Jiang Zhao, Jinsheng He, Liqing Wu, Jingfa Yang, and Yanpeng Zheng
- Subjects
AMYLOID plaque ,STRAWBERRIES ,CLUSTERIN ,DELOCALIZATION energy ,ALZHEIMER'S disease ,FLUORESCENCE resonance energy transfer ,OLIGOMERS - Abstract
Extracellular plaque deposits of ß-amyloid peptide (Aß) are one of the main pathological features of Alzheimer's disease (AD). The aggregation of Aß
42 species, especially Aß42 oligomers, is still an active research field in AD pathogenesis. Secretory clusterin protein (sCLU), an extracellular chaperone, plays an important role in AD pathogenesis. Although sCLU interacts directly with Aß42 in vitro and in vivo, the mechanism is not clear. In this paper, His-tagged sCLU (sCLU-His) was cloned, expressed and purified, and we applied florescence resonance energy transfer-fluorescence correlation spectroscopy (FRET-FCS) to investigate the direct interaction of sCLU-His and Aß42 at the single-molecule fluorescence level in vitro. Here, we chose four different fluorescently labeled Aß42 oligomers to form two different groups of aggregation models, easy or difficult to aggregate. The results showed that sCLU-His could form complexes with both aggregation models, and sCLU-His inhibited the aggregation of Aß42/RB ~ Aß42/Atto647 (easy to aggregate model). The complexes were produced as the Aß42/Label adhered to the sCLU-His, which is similar to a "strawberry model," as strawberry seeds are dotted on the outer surface of strawberries. This work provided additional insight into the interaction mechanism of sCLU and Aß42 . [ABSTRACT FROM AUTHOR]- Published
- 2021
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