Agonist-specific FPR1 conformational change prevents receptor recycling and promotes targeted protein degradation - PubMed
3 hours ago
- #Formyl peptide receptor 1
- #Receptor recycling
- #Protein degradation
- The peptide agonist fMLFC prevents recycling of FPR1, diverting it to late endosomes and lysosomes for degradation.
- In contrast, the classic ligand fMLF facilitates FPR1 recycling by interacting with RAB11 and SNX17.
- A cryo-EM structure reveals key residues (F102, T177, F178) in the fMLFC-bound FPR1-Gi complex; alanine substitutions improve recycling.
- A FlAsH-NanoBRET biosensor shows fMLFC induces a distinct FPR1 conformational change compared to fMLF.
- fMLFC reduces FPR1 cell surface expression and alleviates acute lung injury in LPS-treated mice, acting as a chemical knockdown agent.