View source for 7za2


==GPC3-Unc5D octamer structure and role in cell migration==
<StructureSection load='7za2' size='340' side='right'caption='[[7za2]], [[Resolution|resolution]] 4.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7za2]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ZA2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZA2 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <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=7za2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7za2 OCA], [https://pdbe.org/7za2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7za2 RCSB], [https://www.ebi.ac.uk/pdbsum/7za2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7za2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GPC3_MOUSE GPC3_MOUSE] Cell surface proteoglycan (By similarity). Negatively regulates the hedgehog signaling pathway when attached via the GPI-anchor to the cell surface by competing with the hedgehog receptor PTC1 for binding to hedgehog proteins (PubMed:18477453, PubMed:23665349). Binding to the hedgehog protein SHH triggers internalization of the complex by endocytosis and its subsequent lysosomal degradation (PubMed:18477453). Positively regulates the canonical Wnt signaling pathway by binding to the Wnt receptor Frizzled and stimulating the binding of the Frizzled receptor to Wnt ligands (By similarity). Positively regulates the non-canonical Wnt signaling pathway (PubMed:15537637). Binds to CD81 which decreases the availability of free CD81 for binding to the transcriptional repressor HHEX, resulting in nuclear translocation of HHEX and transcriptional repression (PubMed:23665349). Inhibits the dipeptidyl peptidase activity of DPP4 (By similarity). Plays a role in limb patterning and skeletal development by controlling the cellular response to BMP4 (PubMed:10964473). Modulates the effects of growth factors BMP2, BMP7 and FGF7 on renal branching morphogenesis (PubMed:11180950). Required for coronary vascular development (PubMed:19733558). Plays a role in regulating cell movements during gastrulation (By similarity).[UniProtKB:P51654][UniProtKB:Q6V9Y8]<ref>PMID:10964473</ref> <ref>PMID:11180950</ref> <ref>PMID:15537637</ref> <ref>PMID:18477453</ref> <ref>PMID:19733558</ref> <ref>PMID:23665349</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Neural migration is a critical step during brain development that requires the interactions of cell-surface guidance receptors. Cancer cells often hijack these mechanisms to disseminate. Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. In the complex, four Unc5D molecules pack into an antiparallel bundle, flanked by four GPC3 molecules. Central glycan-glycan interactions are formed by N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains. MD simulations, mass spectrometry and structure-based mutants validate the crystallographic data. Anti-GPC3 nanobodies enhance or weaken Unc5-GPC3 binding and, together with mutant proteins, show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model. The results demonstrate a conserved structural mechanism of cell guidance, where finely balanced Unc5-GPC3 interactions regulate cell migration.

GPC3-Unc5 receptor complex structure and role in cell migration.,Akkermans O, Delloye-Bourgeois C, Peregrina C, Carrasquero-Ordaz M, Kokolaki M, Berbeira-Santana M, Chavent M, Reynaud F, Raj R, Agirre J, Aksu M, White ES, Lowe E, Ben Amar D, Zaballa S, Huo J, Pakos I, McCubbin PTN, Comoletti D, Owens RJ, Robinson CV, Castellani V, Del Toro D, Seiradake E Cell. 2022 Oct 13;185(21):3931-3949.e26. doi: 10.1016/j.cell.2022.09.025. PMID:36240740<ref>PMID:36240740</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7za2" style="background-color:#fffaf0;"></div>

==See Also==
*[[Netrin receptor|Netrin receptor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Rattus norvegicus]]
[[Category: Agirre J]]
[[Category: Akkermans O]]
[[Category: Aksu M]]
[[Category: Ben Amar D]]
[[Category: Berbeira-Santana M]]
[[Category: Carrasquero M]]
[[Category: Castellani V]]
[[Category: Chavent M]]
[[Category: Comoletti D]]
[[Category: Delloye-Bourgeois C]]
[[Category: Huo J]]
[[Category: Kokolaki M]]
[[Category: Lowe E]]
[[Category: McCubbin P]]
[[Category: Owens R]]
[[Category: Pakos I]]
[[Category: Peregrina C]]
[[Category: Reynaud F]]
[[Category: Ritu R]]
[[Category: Robinson C]]
[[Category: Seiradake E]]
[[Category: White E]]
[[Category: Zaballa S]]
[[Category: Del Toro D]]