8XQI

Cryo-EM structure of human dimeric Apelin receptor.

Summary for 8XQI

• Entry DOI: 10.2210/pdb8xqi/pdb
• EMDB information: 38578
• Descriptor: Soluble cytochrome b562,Apelin receptor, CHOLESTEROL (2 entities in total)
• Functional Keywords: gpcr, apelin receptor, dimeric, ligand free., signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 109398.46

Authors

Yue, Y.,Liu, L.E.,Wu, L.J.,Xu, F. (deposition date: 2024-01-05, release date: 2025-01-22)

Primary citation

Yue, Y.,Liu, L.,Wu, L.,Xu, C.,Na, M.,Liu, S.,Liu, Y.,Li, F.,Liu, J.,Shi, S.,Lei, H.,Zhao, M.,Yang, T.,Ji, W.,Wang, A.,Hanson, M.A.,Stevens, R.C.,Liu, J.,Xu, F.
Structural insights into the regulation of monomeric and dimeric apelin receptor.
Nat Commun, 16:310-310, 2025

PubMed Abstract: The apelin receptor (APJR) emerges as a promising drug target for cardiovascular health and muscle regeneration. While prior research unveiled the structural versatility of APJR in coupling to Gi proteins as a monomer or dimer, the dynamic regulation within the APJR dimer during activation remains poorly understood. In this study, we present the structures of the APJR dimer and monomer complexed with its endogenous ligand apelin-13. In the dimeric structure, apelin-13 binds exclusively to one protomer that is coupled with Gi proteins, revealing a distinct ligand-binding behavior within APJR homodimers. Furthermore, binding of an antagonistic antibody induces a more compact dimerization by engaging both protomers. Notably, structural analyses of the APJR dimer complexed with an agonistic antibody, with or without Gi proteins, suggest that G protein coupling may promote the dissociation of the APJR dimer during activation. These findings underscore the intricate interplay between ligands, dimerization, and G protein coupling in regulating APJR signaling pathways.

PubMed: 39747115
DOI: 10.1038/s41467-024-55555-6

Experimental method

ELECTRON MICROSCOPY (3.25 Å)