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From Proteopedia
Cryo-EM structure of human dimeric APJR-Gi complex with apelin-13.
Structural highlights
FunctionAPEL_HUMAN Endogenous ligand for the apelin receptor (APLNR) (PubMed:10525157). Drives internalization of the apelin receptor (By similarity). Apelin-36 dissociates more hardly than (pyroglu)apelin-13 from APLNR (By similarity). Hormone involved in the regulation of cardiac precursor cell movements during gastrulation and heart morphogenesis (By similarity). Has an inhibitory effect on cytokine production in response to T-cell receptor/CD3 cross-linking; the oral intake of apelin in the colostrum and the milk might therefore modulate immune responses in neonates (By similarity). Plays a role in early coronary blood vessels formation (By similarity). Mediates myocardial contractility in an ERK1/2-dependent manner (By similarity). May also have a role in the central control of body fluid homeostasis by influencing vasopressin release and drinking behavior (By similarity).[UniProtKB:Q4TTN8][UniProtKB:Q9R0R3][UniProtKB:Q9R0R4][1] (Microbial infection) Endogenous ligand for the apelin receptor (APLNR), an alternative coreceptor with CD4 for HIV-1 infection (PubMed:11090199). Inhibits HIV-1 entry in cells coexpressing CD4 and APLNR (PubMed:11090199). Apelin-36 has a greater inhibitory activity on HIV infection than other synthetic apelin derivatives (PubMed:11090199).[2] Publication Abstract from PubMedThe 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Liu LE | Wu LJ | Xu F | Yue Y
