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Clusterin inhibits Aβ 42 aggregation through a “strawberry model” as detected by FRET‐FCS
Author(s) -
Xu Lingwan,
Tian Shijun,
Peng Xianglei,
Hua Ying,
Yang Wenxuan,
Chen Longwei,
Liu Shilei,
Wu Wenzheng,
Zhao Jiang,
He Jinsheng,
Wu Liqing,
Yang Jingfa,
Zheng Yanpeng
Publication year - 2021
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.15344
Subject(s) - clusterin , chemistry , förster resonance energy transfer , biophysics , in vitro , in vivo , protein aggregation , amyloid (mycology) , fluorescence , extracellular , microbiology and biotechnology , biochemistry , biology , apoptosis , inorganic chemistry , physics , quantum mechanics
Extracellular plaque deposits of β‐amyloid peptide (Aβ) are one of the main pathological features of Alzheimer's disease (AD). The aggregation of Aβ 42 species, especially Aβ 42 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 Aβ 42 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 Aβ 42 at the single‐molecule fluorescence level in vitro. Here, we chose four different fluorescently labeled Aβ 42 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 Aβ 42/RB ~ Aβ 42/Atto647 (easy to aggregate model). The complexes were produced as the Aβ 42/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 Aβ 42 .