View source for 9kux


==Cryo-EM structure of dimeric APJR and one Beta-arrestin complex with small molecules==
<StructureSection load='9kux' size='340' side='right'caption='[[9kux]], [[Resolution|resolution]] 3.57&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9kux]] is a 3 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=9KUX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9KUX 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]] 3.57&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1L6R:(1~{S},2~{S})-~{N}-[4-(2,6-dimethoxyphenyl)-5-(6-methylpyridin-2-yl)-1,2,4-triazol-3-yl]-1-(5-methylpyrimidin-2-yl)-1-oxidanyl-propane-2-sulfonamide'>A1L6R</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></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=9kux FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9kux OCA], [https://pdbe.org/9kux PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9kux RCSB], [https://www.ebi.ac.uk/pdbsum/9kux PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9kux ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The 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<ref>PMID:40790299</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9kux" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Wu LJ]]
[[Category: Xu F]]
[[Category: Yue Y]]