View source for 21kr


==A Wnt3a/Fzd8-CRD/LRP6-E3E4 complex with FKBP==
<StructureSection load='21kr' size='340' side='right'caption='[[21kr]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[21kr]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=21KR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=21KR 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]] 2.9&#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>, <scene name='pdbligand=RAP:RAPAMYCIN+IMMUNOSUPPRESSANT+DRUG'>RAP</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=21kr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=21kr OCA], [https://pdbe.org/21kr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=21kr RCSB], [https://www.ebi.ac.uk/pdbsum/21kr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=21kr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/WNT3A_MOUSE WNT3A_MOUSE] Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/LEF family (PubMed:26902720). Required for normal embryonic mesoderm development and formation of caudal somites (PubMed:8299937). Required for normal morphogenesis of the developing neural tube (PubMed:8299937). Mediates self-renewal of the stem cells at the bottom on intestinal crypts (in vitro) (PubMed:26902720).<ref>PMID:26902720</ref> <ref>PMID:8299937</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Recognition of Wnt proteins by Frizzled (Fzd) receptors and the low-density lipoprotein receptor-related protein 5/6 (LRP5/6) co-receptor is essential for canonical Wnt signaling. It remains enigmatic how Wnt simultaneously interacts with Fzd and LRP5/6 and activates intracellular Wnt/beta-catenin signaling. Here, we report cryo-electron microscopy (cryo-EM) structures of Wnt3a/Fzd8/LRP6 extracellular complexes captured in a 2:4:2 stoichiometry, consisting of a Wnt3a-Wnt3a homodimer, whereby each Wnt3a monomer binds to two Fzd8 receptors and one LRP6 co-receptor. This implies that Wnt3a induces Fzd cystine-rich domain (Fzd-CRD) tetramerization, which in turn could promote recruitment of oligomeric Disheveled (Dvl) to Fzd on the cytoplasmic side. Indeed, mutations of key Wnt3a-Wnt3a interface residues abolish Fzd-LRP clustering and downstream signaling, supporting a critical role of Wnt3a-Wnt3a dimerization in Wnt signalosome assembly and signaling. Our structures also show how the Wnt3a N-helical domain recognizes the LRP6 extracellular domain (LRP6-ECD) E3 beta-propeller, while the Wnt3a N-C hairpin interacts with the valley between LRP6-E3 and -E4 propellers, underpinning the development of targeted Wnt therapeutics.

Structural basis of Wnt signalosome extracellular complex assembly.,Yue D, Sun G, Cao Y, Li H, Yang Y, Pan Z, Xue L, Zhang L, Wang Z, Xu W Cell. 2026 May 27:S0092-8674(26)00523-4. doi: 10.1016/j.cell.2026.05.006. PMID:42202788<ref>PMID:42202788</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 21kr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Sun G]]
[[Category: Wang Z]]
[[Category: Xu W]]
[[Category: Yue D]]
[[Category: Zhang L]]