A co-assembly platform engaging macrophage scavenger receptor A for lysosome-targeting protein degradation

Qian Wang, Xingyue Yang, Ruixin Yuan, Ao Shen, Pushu Wang, Haoting Li, Jun Zhang, Chao Tian, Zhujun Jiang, Wenzhe Li and Suwei Dong ()
Additional contact information
Qian Wang: Peking University
Xingyue Yang: Peking University
Ruixin Yuan: Peking University
Ao Shen: Peking University
Pushu Wang: Peking University
Haoting Li: Peking University
Jun Zhang: Peking University
Chao Tian: Peking University
Zhujun Jiang: Peking University
Wenzhe Li: Peking University
Suwei Dong: Peking University

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-46130-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46130-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-46130-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().