8xqe

From Proteopedia

(Difference between revisions)

Current revision

Cryo-EM structure of human dimeric APJR-Gi complex with apelin-13.

Structural highlights

8xqe is a 7 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 3.48Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

APEL_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 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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Habata Y, Fujii R, Hosoya M, Fukusumi S, Kawamata Y, Hinuma S, Kitada C, Nishizawa N, Murosaki S, Kurokawa T, Onda H, Tatemoto K, Fujino M. Apelin, the natural ligand of the orphan receptor APJ, is abundantly secreted in the colostrum. Biochim Biophys Acta. 1999 Oct 13;1452(1):25-35. PMID:10525157 doi:10.1016/s0167-4889(99)00114-7
↑ Cayabyab M, Hinuma S, Farzan M, Choe H, Fukusumi S, Kitada C, Nishizawa N, Hosoya M, Nishimura O, Messele T, Pollakis G, Goudsmit J, Fujino M, Sodroski J. Apelin, the natural ligand of the orphan seven-transmembrane receptor APJ, inhibits human immunodeficiency virus type 1 entry. J Virol. 2000 Dec;74(24):11972-6. PMID:11090199 doi:10.1128/jvi.74.24.11972-11976.2000
↑ 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. Structural insights into the regulation of monomeric and dimeric apelin receptor. Nat Commun. 2025 Jan 2;16(1):310. PMID:39747115 doi:10.1038/s41467-024-55555-6

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8xqe"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8xqe is ON HOLD  until Paper Publication
+==Cryo-EM structure of human dimeric APJR-Gi complex with apelin-13.==
+<StructureSection load='8xqe' size='340' side='right'caption='[[8xqe]], [[Resolution|resolution]] 3.48&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8xqe]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8XQE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8XQE FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.48&#8491;</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8xqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8xqe OCA], [https://pdbe.org/8xqe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8xqe RCSB], [https://www.ebi.ac.uk/pdbsum/8xqe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8xqe ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/APEL_HUMAN APEL_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]<ref>PMID:10525157</ref>   (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).<ref>PMID:11090199</ref>
+<div style="background-color:#fffaf0;">
+== 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.
-Authors:
+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<ref>PMID:39747115</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8xqe" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Liu LE]]
+[[Category: Wu LJ]]
+[[Category: Xu F]]
+[[Category: Yue Y]]

8xqe

From Proteopedia

Current revision

Cryo-EM structure of human dimeric APJR-Gi complex with apelin-13.

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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