Structural highlights
Publication Abstract from PubMedThe apelin receptor (APJR) plays a pivotal role in regulating cardiovascular and metabolic health(1,2). Understanding the mechanisms of biased agonism at APJR is crucial for drug discovery, as stimulation of the beta-arrestin pathway may lead to some adverse effects(3). Structural analyses of APJR-Gi complexes have clarified the structural basis of receptor dimerization and activation(4,5), yet the absence of structural data on APJR-arrestin complexes has impeded a comprehensive understanding of APJR stoichiometry in the dual signaling pathways and biased agonism. Here, we present APJR-beta-arrestin1 structures bound to a clinical drug analog, revealing 2:2 and 2:1 stoichiometries associated with differential beta-arrestin recruitment. Through comparison of the two transducer-coupled APJR structures bound to the same ligand, we identify key residues and motifs crucial for directing biased signaling. These findings highlight APJR's versatile stoichiometry in coupling with beta-arrestin and Gi proteins, establishing a framework for understanding biased agonism and guiding the development of therapeutics. Mechanistic insights into the versatile stoichiometry and biased signaling of the apelin receptor-arrestin complex.,Yue Y, Xu C, Wu L, Na M, Xu K, Chen X, Song Y, Weng S, Xu L, Li F, Lin X, Wang A, Liu J, Xu F Nat Commun. 2025 Aug 11;16(1):7403. doi: 10.1038/s41467-025-62870-z. PMID:40790299[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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This page was last modified 05:38, 17 September 2025.