Design of Multimodal Supramolecular Protein Assemblies via Enzyme-Substrate Interactions for Intracellular Antioxidant Regulation.

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Tác giả: Yan Ge, Chunxi Hou, Cong Li, Hui Li, Yujun Li, Junqiu Liu, Zhenhui Qi, Tingting Wang, Jiarun Wu, Yaqi Wu, Jiayun Xu, Zhengwei Xu, Xiaoxuan Yu

Ngôn ngữ: eng

Ký hiệu phân loại: 220.5207 Modern versions and translations

Thông tin xuất bản: United States : Nano letters , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 686960

Allosteric modulation of protein function, which involves effector binding triggering distant conformational changes, is crucial for cellular and metabolic control. However, achieving tunable control, structural diversity, and precise intracellular regulation remains challenging. Here, we designed dynamic supramolecular protein assemblies driven by enzyme-substrate interactions for antioxidant regulation in cells. Using a glutathione S-transferase modified with a cysteine mutation (GSTK77C), we engineered an effector molecule (GMP4M) containing a glutathione (GSH) moiety and maleimide group linked by a PEG chain. This system forms hierarchical protein assemblies with diverse morphologies, including nanowires, nanorings, nanobranches, and nanotwists, and switchable "ON/OFF" enzymatic activity modulated by endogenous GSH. The assemblies maintain structural integrity under physiological conditions, show remarkable reversibility, and outperform native GST in stability and environmental adaptability. This approach provides a versatile platform for creating tunable and diverse protein assemblies with broad applications in antioxidant therapies and biomedical interventions.
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