溶酶体
清道夫受体
去唾液酸糖蛋白受体
蛋白质降解
细胞生物学
膜蛋白
化学
受体
细胞外
细胞表面受体
生物化学
生物
膜
胆固醇
脂蛋白
体外
酶
肝细胞
作者
Qin Wang,Xingyue Yang,Ruixin Yuan,Ao Shen,Pushu Wang,Haoting Li,Jun Zhang,Chao Tian,Zhujun Jiang,Wenzhe Li,Suwei Dong
标识
DOI:10.1038/s41467-024-46130-0
摘要
Targeted degradation of proteins has emerged as a powerful method for modulating protein homeostasis. Identification of suitable degraders is essential for achieving effective protein degradation. Here, we present a non-covalent degrader construction strategy, based on a modular supramolecular co-assembly system consisting of two self-assembling peptide ligands that bind cell membrane receptors and the protein of interest simultaneously, resulting in targeted protein degradation. The developed lysosome-targeting co-assemblies (LYTACAs) can induce lysosomal degradation of extracellular protein IL-17A and membrane protein PD-L1 in several scavenger receptor A-expressing cell lines. The IL-17A-degrading co-assembly has been applied in an imiquimod-induced psoriasis mouse model, where it decreases IL-17A levels in the skin lesion and alleviates psoriasis-like inflammation. Extending to asialoglycoprotein receptor-related protein degradation, LYTACAs have demonstrated the versatility and potential in streamlining degraders for extracellular and membrane proteins.
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