Endosome-phagophore linking assemblies for the degradation of membrane/extracellular proteins.

ABSTRACT: Lysosome-targeting chimeras specifically degrade membrane/extracellular proteins with the specificity and potency highly dependent on the expression pattern and kinetics of lysosome-targeting receptors. Here we describe an endosome-phagophore linking assembly (EPLA), which is constructed by attaching a specific ligand for a protein of interest (POI) to an endosome surface-anchored phagophore-targeting peptide (ES-PTP) that consists of a pH-low insertion peptide and a phagophore-binding element. EPLAs degrade proteins by binding with POIs, being internalized into endosomes, inserting endosome membrane, anchoring the phagophore-targeting moiety onto endosome surface, and then triggering the spatial proximity of endosomes to phagophores. We show the modularity and generality of the EPLA techn

SUBMITTER: Wang P 

PROVIDER: S-EPMC12748777 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature