View source for 9kb9


==Cryo-EM structure of LGR4-RSPO2-ZNRF3 complex (2:2:2)==
<StructureSection load='9kb9' size='340' side='right'caption='[[9kb9]], [[Resolution|resolution]] 3.59&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9kb9]] is a 6 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=9KB9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9KB9 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]] 3.59&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=9kb9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9kb9 OCA], [https://pdbe.org/9kb9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9kb9 RCSB], [https://www.ebi.ac.uk/pdbsum/9kb9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9kb9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LGR4_HUMAN LGR4_HUMAN] Orphan receptor.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) plays a critical role in regulating the wingless-related integration site (Wnt) signaling pathway and is essential for organ development and carcinogenesis. LGR4, along with its ligand R-spondin (RSPO), potentiates Wnt/beta-catenin signaling by recruiting its signaling suppressor, E3 ligase Zinc and Ring Finger 3 (ZNRF3), and inducing its membrane clearance. However, detailed mechanisms underlying this process remain unknown. In this study, we present the cryo-electron microscopy structures of human LGR4, the LGR4-RSPO2 and LGR4-RSPO2-ZNRF3 complexes. Upon RSPO2 binding, LGR4 undergoes no significant conformational changes in its transmembrane and extracellular domain structures or their relative orientations. LGR4, RSPO2, and ZNRF3 assemble into a 2:2:2 complex with the ZNRF3 dimer enclosed at the center. This ternary arrangement and forced dimerization of ZNRF3 likely underpin how LGR4 and RSPO2 potentiate Wnt/beta-catenin signaling by sequestering ZNRF3 from Wnt receptors and facilitating its auto-inactivation. This study provides a structural basis for understanding the regulatory mechanism of Wnt/beta-catenin signaling through the LGR4-RSPO2-ZNRF3 pathway and may offer opportunities for future drug development targeting this axis.

Structural insights into Wnt/beta-catenin signaling regulation by LGR4, R-spondin, and ZNRF3.,Peng Y, Fujimura A, Asami J, Zhang Z, Shimizu T, Ohto U Nat Commun. 2025 Oct 1;16(1):8337. doi: 10.1038/s41467-025-64129-z. PMID:41034211<ref>PMID:41034211</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9kb9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Asami J]]
[[Category: Fujimura A]]
[[Category: Ohto U]]
[[Category: Peng Y]]
[[Category: Shimizu T]]
[[Category: Zhang Z]]