at Peking University School of Pharmaceutical Sciences
​​​​the dong research group
38. A co-assembly platform engaging macrophage scavenger receptor A for lysosome-targeting protein degradation
Nat Commun 15, 1663 (2024).
Qian Wang, Xingyue Yang, Ruixin Yuan, Ao Shen, Pushu Wang, Haoting Li, Jun Zhang, Chao Tian, Zhujun Jiang, Wenzhe Li & Suwei Dong*

Fig. 6

figure 6

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.