8z7j

Cryo-EM structure of APJR-Gi complex with agonistic antibody

spinqualitylabelsall models 8z7j, resolution 3.12Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8z7j is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.12Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GNAI1_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division. Publication Abstract from PubMed 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. Structural insights into the regulation of monomeric and dimeric apelin receptor.,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 MA, Stevens RC, Liu J, Xu F Nat Commun. 2025 Jan 2;16(1):310. doi: 10.1038/s41467-024-55555-6. PMID:39747115 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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