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| | <StructureSection load='4c84' size='340' side='right'caption='[[4c84]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='4c84' size='340' side='right'caption='[[4c84]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4c84]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C84 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C84 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4c84]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C84 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C84 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c85|4c85]], [[4c86|4c86]], [[4c8a|4c8a]], [[4c8c|4c8c]], [[4c8f|4c8f]], [[4c8p|4c8p]], [[4c8t|4c8t]], [[4c8u|4c8u]], [[4c8v|4c8v]], [[4c8w|4c8w]], [[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]] 1.6Å</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=4c84 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c84 OCA], [http://pdbe.org/4c84 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4c84 RCSB], [http://www.ebi.ac.uk/pdbsum/4c84 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4c84 ProSAT]</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=4c84 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c84 OCA], [https://pdbe.org/4c84 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c84 RCSB], [https://www.ebi.ac.uk/pdbsum/4c84 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c84 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Function == | |
| - | [[http://www.uniprot.org/uniprot/ZNRF3_DANRE ZNRF3_DANRE]] E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination and subsequent degradation of Wnt receptor complex components. | |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Ubiquitin protein ligase|Ubiquitin protein ligase]] | + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Brachidanio rerio]] | + | [[Category: Danio rerio]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Jones, E Y]] | + | [[Category: Jones EY]] |
| - | [[Category: Zebisch, M]] | + | [[Category: Zebisch M]] |
| - | [[Category: Lgr4]]
| + | |
| - | [[Category: Lgr5]]
| + | |
| - | [[Category: Lgr6]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: R-spo]]
| + | |
| - | [[Category: R-spondin]]
| + | |
| - | [[Category: Receptor]]
| + | |
| - | [[Category: Rnf43]]
| + | |
| - | [[Category: Rspo]]
| + | |
| - | [[Category: Rspo1]]
| + | |
| - | [[Category: Rspo2]]
| + | |
| - | [[Category: Rspo3]]
| + | |
| - | [[Category: Rspo4]]
| + | |
| - | [[Category: Signalling]]
| + | |
| - | [[Category: Wnt]]
| + | |
| Structural highlights
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.
See Also
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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