4f0a

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{{STRUCTURE_4f0a| PDB=4f0a | SCENE= }}
 
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===Crystal structure of XWnt8 in complex with the cysteine-rich domain of Frizzled 8===
 
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{{ABSTRACT_PUBMED_22653731}}
 
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==Function==
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==Crystal structure of XWnt8 in complex with the cysteine-rich domain of Frizzled 8==
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[[http://www.uniprot.org/uniprot/FZD8_MOUSE FZD8_MOUSE]] Receptor for Wnt proteins. Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalsomes (By similarity). The beta-catenin canonical signaling pathway leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Coreceptor along with RYK of Wnt proteins, such as WNT1.<ref>PMID:10395542</ref> <ref>PMID:10097073</ref> <ref>PMID:15454084</ref> <ref>PMID:16543246</ref>
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<StructureSection load='4f0a' size='340' side='right'caption='[[4f0a]], [[Resolution|resolution]] 3.25&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4f0a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F0A FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.25&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PAM:PALMITOLEIC+ACID'>PAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4f0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f0a OCA], [https://pdbe.org/4f0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f0a RCSB], [https://www.ebi.ac.uk/pdbsum/4f0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f0a ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/FZD8_MOUSE FZD8_MOUSE] Receptor for Wnt proteins. Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalsomes (By similarity). The beta-catenin canonical signaling pathway leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Coreceptor along with RYK of Wnt proteins, such as WNT1.<ref>PMID:10395542</ref> <ref>PMID:10097073</ref> <ref>PMID:15454084</ref> <ref>PMID:16543246</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Wnts are lipid-modified morphogens that play critical roles in development principally through engagement of Frizzled receptors. The 3.25 A structure of Xenopus Wnt8 (XWnt8) in complex with mouse Frizzled-8 cysteine-rich domain (CRD) reveals an unusual two-domain Wnt structure, not obviously related to known protein folds, resembling a "hand" with "thumb" and "index" fingers extended to grasp the Fz8-CRD at two distinct binding sites. One site is dominated by a palmitoleic acid lipid group projecting from Serine 187 at the tip of Wnt's thumb into a deep groove in the Fz8-CRD. In the second binding site, the conserved tip of Wnt's "index finger" forms hydrophobic amino acid contacts with a depression on the opposite side of the Fz8-CRD. The conservation of amino acids in both interfaces appears to facilitate ligand-receptor cross-reactivity, which has important implications for understanding Wnt's functional pleiotropy and for developing Wnt-based drugs for cancer and regenerative medicine.
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==About this Structure==
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Structural Basis of Wnt Recognition by Frizzled.,Janda CY, Waghray D, Levin AM, Thomas C, Garcia KC Science. 2012 May 31. PMID:22653731<ref>PMID:22653731</ref>
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[[4f0a]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F0A OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:022653731</ref><references group="xtra"/><references/>
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</div>
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<div class="pdbe-citations 4f0a" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Xenopus laevis]]
[[Category: Xenopus laevis]]
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[[Category: Garcia, K C.]]
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[[Category: Garcia KC]]
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[[Category: Janda, C Y.]]
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[[Category: Janda CY]]
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[[Category: Levin, A M.]]
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[[Category: Levin AM]]
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[[Category: Thomas, C.]]
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[[Category: Thomas C]]
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[[Category: Waghray, D.]]
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[[Category: Waghray D]]
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[[Category: Fatty acid acylation]]
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[[Category: Frizzled]]
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[[Category: Glycosylation]]
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[[Category: Ligand-receptor complex]]
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[[Category: Signaling protein]]
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[[Category: Wnt]]
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[[Category: Wnt signaling]]
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Current revision

Crystal structure of XWnt8 in complex with the cysteine-rich domain of Frizzled 8

PDB ID 4f0a

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