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| | <StructureSection load='6ahy' size='340' side='right'caption='[[6ahy]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='6ahy' size='340' side='right'caption='[[6ahy]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ahy]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AHY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AHY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ahy]] is a 6 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=6AHY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AHY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PAM:PALMITOLEIC+ACID'>PAM</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PAM:PALMITOLEIC+ACID'>PAM</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Fzd8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), WNT3, INT4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6ahy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ahy OCA], [https://pdbe.org/6ahy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ahy RCSB], [https://www.ebi.ac.uk/pdbsum/6ahy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ahy ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ahy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ahy OCA], [http://pdbe.org/6ahy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ahy RCSB], [http://www.ebi.ac.uk/pdbsum/6ahy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ahy ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/WNT3_HUMAN WNT3_HUMAN]] Tetraamelia-multiple malformations syndrome. The disease is caused by mutations affecting the gene represented in this entry. | |
| | == Function == | | == Function == |
| - | [[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> [[http://www.uniprot.org/uniprot/WNT3_HUMAN WNT3_HUMAN]] 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 gastrulation, formation of the primitive streak, and for the formation of the mesoderm during early embryogenesis. Required for normal formation of the apical ectodermal ridge (By similarity). Required for normal embryonic development, and especially for limb development (PubMed:14872406).[UniProtKB:P17553]<ref>PMID:14872406</ref> <ref>PMID:26902720</ref> | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Arimori, T]] | + | [[Category: Arimori T]] |
| - | [[Category: Hirai, H]] | + | [[Category: Hirai H]] |
| - | [[Category: Matoba, K]] | + | [[Category: Matoba K]] |
| - | [[Category: Mihara, E]] | + | [[Category: Mihara E]] |
| - | [[Category: Takagi, J]] | + | [[Category: Takagi J]] |
| - | [[Category: Canonical wnt pathway]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Wnt signaling]]
| + | |
| Structural highlights
Function
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.[1] [2] [3] [4]
Publication Abstract from PubMed
Wnt signaling plays fundamental roles in organogenesis, tissue regeneration and cancer, but high-resolution structural information of mammalian Wnt proteins is lacking. We solved a 2.8-A resolution crystal structure of human Wnt3 in complex with mouse Frizzled 8 Cys-rich domain (CRD). Wnt3 grabs the receptor in a manner very similar to that found in Xenopus Wnt8 complexed with the same receptor. Unlike Xenopus Wnt8-bound CRD, however, Wnt3-bound CRD formed a symmetrical dimer in the crystal by exchanging the tip of the unsaturated acyl chain attached to each Wnt3, confirming the ability of Wnt and Frizzled CRD to form a 2:2 complex. The hypervariable 'linker' region of Wnt3 formed a beta-hairpin protrusion opposite from the Frizzled binding interface, consistent with its proposed role in the coreceptor recognition. Direct binding between this segment and the Wnt coreceptor LRP6 was confirmed, enabling us to build a structural model of the Wnt-Frizzled-LRP6 ternary complex.
Crystal structure of a mammalian Wnt-frizzled complex.,Hirai H, Matoba K, Mihara E, Arimori T, Takagi J Nat Struct Mol Biol. 2019 May;26(5):372-379. doi: 10.1038/s41594-019-0216-z. Epub, 2019 Apr 29. PMID:31036956[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sheldahl LC, Park M, Malbon CC, Moon RT. Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner. Curr Biol. 1999 Jul 1;9(13):695-8. PMID:10395542
- ↑ Hsieh JC, Rattner A, Smallwood PM, Nathans J. Biochemical characterization of Wnt-frizzled interactions using a soluble, biologically active vertebrate Wnt protein. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3546-51. PMID:10097073
- ↑ Lu W, Yamamoto V, Ortega B, Baltimore D. Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth. Cell. 2004 Oct 1;119(1):97-108. PMID:15454084 doi:10.1016/j.cell.2004.09.019
- ↑ Nam JS, Turcotte TJ, Smith PF, Choi S, Yoon JK. Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled 8 and LRP6 receptors and activate beta-catenin-dependent gene expression. J Biol Chem. 2006 May 12;281(19):13247-57. Epub 2006 Mar 16. PMID:16543246 doi:10.1074/jbc.M508324200
- ↑ Hirai H, Matoba K, Mihara E, Arimori T, Takagi J. Crystal structure of a mammalian Wnt-frizzled complex. Nat Struct Mol Biol. 2019 May;26(5):372-379. doi: 10.1038/s41594-019-0216-z. Epub, 2019 Apr 29. PMID:31036956 doi:http://dx.doi.org/10.1038/s41594-019-0216-z
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