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An Artificial Chaperone Serves a Dual Role in Regulating the Assembly of Peptides through Phase Separation
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  • Wang Li,
  • Yang Zhou,
  • Sheng He,
  • Congsen Wang,
  • Peichen Shi,
  • Suixu Li,
  • Xinchang Wang,
  • Liulin Yang,
  • Xiao-Yu Cao,
  • Zhong-Qun Tian
Wang Li
Xiamen University
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Yang Zhou
Xiamen University
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Sheng He
Xiamen University
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Congsen Wang
Xiamen University
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Peichen Shi
Xiamen University
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Suixu Li
Xiamen University
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Xinchang Wang
Xiamen University
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Liulin Yang
Xiamen University

Corresponding Author:[email protected]

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Xiao-Yu Cao
Xiamen University
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Zhong-Qun Tian
Xiamen University
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Abstract

In biological systems, molecular assembly primarily relies on the assistance of molecular chaperones. Inspired by nature, strategies like ‘chaperone-assisted assembly’ and ‘catalyzed assembly’ have been proposed towards the sophisticated control of molecular assembly. Nonetheless, significant challenges remain in the rational design of such systems, calling for a deep understanding of underlying principles. Herein, we demonstrate an artificial chaperone serves a dual role, i.e. catalyst in low dosages and inhibitor in high dosages, in regulating the supramolecular polymerization of peptides. Low dosages of carboxymethyl cellulose, as the chaperones, catalyse the assembly of Aβ16-22 peptides into fibrils through multi-step phase separation, while high dosages trap the peptides into coacervate intermediates and therefore inhibit the fibrillation. Consequently, the quantity of chaperone does not follow the intuition that ‘more is better’ for catalyzing assembly, but instead has an optimal molar ratio. Investigation reveals that the interplay and evolution of electrostatic and hydrophobic interactions between chaperones and peptides are the keys to achieving these processes. This study provides insights into the multifaceted roles artificial chaperones may play in a dosage-dependent manner, and enriches the toolkit for efficient and controllable construction of complex assembly systems.
27 Sep 2023Submitted to Aggregate
28 Sep 2023Assigned to Editor
28 Sep 2023Submission Checks Completed
29 Sep 2023Reviewer(s) Assigned