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| | ==Xenopus RSPO2 Fu1-Fu2 crystal form II== | | ==Xenopus RSPO2 Fu1-Fu2 crystal form II== |
| - | <StructureSection load='4c8w' size='340' side='right' caption='[[4c8w]], [[Resolution|resolution]] 3.10Å' scene=''> | + | <StructureSection load='4c8w' size='340' side='right'caption='[[4c8w]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4c8w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Silurana_(xenopus)_tropicalis Silurana (xenopus) tropicalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C8W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C8W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4c8w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_tropicalis Xenopus tropicalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C8W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C8W FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c84|4c84]], [[4c85|4c85]], [[4c86|4c86]], [[4c8a|4c8a]], [[4c8c|4c8c]], [[4c8f|4c8f]], [[4c8p|4c8p]], [[4c8t|4c8t]], [[4c8u|4c8u]], [[4c8v|4c8v]], [[4c99|4c99]], [[4c9a|4c9a]], [[4c9e|4c9e]], [[4c9r|4c9r]], [[4c9u|4c9u]], [[4c9v|4c9v]]</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]] 3.1Å</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=4c8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c8w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4c8w RCSB], [http://www.ebi.ac.uk/pdbsum/4c8w PDBsum]</span></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=4c8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c8w OCA], [https://pdbe.org/4c8w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c8w RCSB], [https://www.ebi.ac.uk/pdbsum/4c8w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c8w ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RSPO2_XENTR RSPO2_XENTR]] Activator of the canonical Wnt signaling pathway by acting as a ligand for lgr4-6 receptors. Upon binding to lgr4-6 (lgr4, lgr5 or lgr6), lgr4-6 associate with phosphorylated lrp6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Acts both in the canonical. Wnt/beta-catenin-dependent pathway and in non-canonical Wnt signaling pathway. Activates neural markers and promotes muscle formation. Overexpression blocks activin, nodal and BMP4 signaling, suggesting that it may negatively regulate the TGF-beta pathway (By similarity). | + | [https://www.uniprot.org/uniprot/RSPO2_XENTR RSPO2_XENTR] Activator of the canonical Wnt signaling pathway by acting as a ligand for lgr4-6 receptors. Upon binding to lgr4-6 (lgr4, lgr5 or lgr6), lgr4-6 associate with phosphorylated lrp6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Acts both in the canonical. Wnt/beta-catenin-dependent pathway and in non-canonical Wnt signaling pathway. Activates neural markers and promotes muscle formation. Overexpression blocks activin, nodal and BMP4 signaling, suggesting that it may negatively regulate the TGF-beta pathway (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4c8w" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Jones, E Y]] | + | [[Category: Large Structures]] |
| - | [[Category: Zebisch, M]] | + | [[Category: Xenopus tropicalis]] |
| - | [[Category: Lgr4]] | + | [[Category: Jones EY]] |
| - | [[Category: Lgr5]] | + | [[Category: Zebisch M]] |
| - | [[Category: Lgr6]]
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| - | [[Category: Membrane]]
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| - | [[Category: R-spo]]
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| - | [[Category: Receptor]]
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| - | [[Category: Rnf43]]
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| - | [[Category: Rspo]]
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| - | [[Category: Rspo1]]
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| - | [[Category: Rspo3]]
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| - | [[Category: Rspo4]]
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| - | [[Category: Signaling protein]]
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| - | [[Category: Signalling]]
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| - | [[Category: Wnt]]
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| - | [[Category: Znrf3]]
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| Structural highlights
Function
RSPO2_XENTR Activator of the canonical Wnt signaling pathway by acting as a ligand for lgr4-6 receptors. Upon binding to lgr4-6 (lgr4, lgr5 or lgr6), lgr4-6 associate with phosphorylated lrp6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Acts both in the canonical. Wnt/beta-catenin-dependent pathway and in non-canonical Wnt signaling pathway. Activates neural markers and promotes muscle formation. Overexpression blocks activin, nodal and BMP4 signaling, suggesting that it may negatively regulate the TGF-beta pathway (By similarity).
Publication Abstract from PubMed
The four R-spondin (Rspo) proteins are secreted agonists of Wnt signalling in vertebrates, functioning in embryogenesis and adult stem cell biology. Through ubiquitination and degradation of Wnt receptors, the transmembrane E3 ubiquitin ligase ZNRF3 and related RNF43 antagonize Wnt signalling. Rspo ligands have been reported to inhibit the ligase activity through direct interaction with ZNRF3 and RNF43. Here we report multiple crystal structures of the ZNRF3 ectodomain (ZNRF3ecto), a signalling-competent Furin1-Furin2 (Fu1-Fu2) fragment of Rspo2 (Rspo2Fu1-Fu2), and Rspo2Fu1-Fu2 in complex with ZNRF3ecto, or RNF43ecto. A prominent loop in Fu1 clamps into equivalent grooves in the ZNRF3ecto and RNF43ecto surface. Rspo binding enhances dimerization of ZNRF3ecto but not of RNF43ecto. Comparison of the four Rspo proteins, mutants and chimeras in biophysical and cellular assays shows that their signalling potency depends on their ability to recruit ZNRF3 or RNF43 via Fu1 into a complex with LGR receptors, which interact with Rspo via Fu2.
Structural and molecular basis of ZNRF3/RNF43 transmembrane ubiquitin ligase inhibition by the Wnt agonist R-spondin.,Zebisch M, Xu Y, Krastev C, Macdonald BT, Chen M, Gilbert RJ, He X, Jones EY Nat Commun. 2013 Nov 14;4:2787. doi: 10.1038/ncomms3787. PMID:24225776[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zebisch M, Xu Y, Krastev C, Macdonald BT, Chen M, Gilbert RJ, He X, Jones EY. Structural and molecular basis of ZNRF3/RNF43 transmembrane ubiquitin ligase inhibition by the Wnt agonist R-spondin. Nat Commun. 2013 Nov 14;4:2787. doi: 10.1038/ncomms3787. PMID:24225776 doi:http://dx.doi.org/10.1038/ncomms3787
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