Agonist-specific FPR1 conformational change prevents receptor recycling and promotes targeted protein degradation.

Junlin Wang, Qiwen Liao, Geng Chen, Yixin Chang, Hong Nie, Jiahong Lu, Richard D Ye

Abstract read

In one paragraph

Article in Acta pharmaceutica Sinica. B, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Junlin WangState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, College of Pharmacy, Jinan University, Guangzhou 510632, China.

Qiwen LiaoKobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China.

Geng ChenKobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China.

Yixin ChangKobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China.

Hong NieState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, College of Pharmacy, Jinan University, Guangzhou 510632, China.

Jiahong LuState Key Laboratory of Mechanism and Quality of Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR 999078, China.

Richard D YeKobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recycling of internalized cell surface receptors is critical for membrane transport and receptor-mediated signaling. Formyl peptide receptor 1 (FPR1) plays important roles in host defense and inflammatory tissue injury. Here we report that fMet-Leu-Phe-Cys (fMLFC), a peptide agonist of FPR1, prevents recycling of internalized FPR1 and diverts it to the late endosome and lysosome for degradation. In contrast, FPR1 bound to the classic ligand fMLF interacts with RAB11 and SNX17, facilitating its recycling back to the cell surface. We determined a cryo-EM structure of fMLFC-bound FPR1-Gi complex. Alanine substitutions of key residues that interact with fMLFC (F102A, T177A, F178A) improved FPR1 recycling. Using a FlAsH-NanoBRET-based FPR1 biosensor, the fMLFC-induced receptor conformational change was found to be different from the fMLF-induced conformational change. fMLFC stimulation reduced FPR1 cell surface expression, along with reduced acute lung injury in LPS-treated mice. Our findings suggest that fMLFC is a chemical knockdown agent that promotes targeted protein degradation and reduces FPR1-mediated inflammation.

Indexed as

Acute lung injuryCryo-EMFormyl peptide receptorsG protein-coupled receptorsProtein degradationReceptor recyclingSmall GTPasesSorting nexins

Identifiers

PMID42180545

DOI10.1016/j.apsb.2026.03.019

PMCPMC13198294

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.