4cdj: Difference between revisions

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<StructureSection load='4cdj' size='340' side='right'caption='[[4cdj]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
<StructureSection load='4cdj' size='340' side='right'caption='[[4cdj]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4cdj]] is a 2 chain structure with sequence from [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=4CDJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CDJ FirstGlance]. <br>
<table><tr><td colspan='2'>[[4cdj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CDJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CDJ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cdk|4cdk]]</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=4cdj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cdj OCA], [https://pdbe.org/4cdj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cdj RCSB], [https://www.ebi.ac.uk/pdbsum/4cdj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cdj 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=4cdj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cdj OCA], [http://pdbe.org/4cdj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cdj RCSB], [http://www.ebi.ac.uk/pdbsum/4cdj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cdj ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/ZNRF3_MOUSE ZNRF3_MOUSE]] 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 Frizzled and LRP6. Acts on both canonical and non-canonical Wnt signaling pathway. Acts as a tumor suppressor in the intestinal stem cell zone by inhibiting the Wnt signaling pathway, thereby resticting the size of the intestinal stem cell zone.<ref>PMID:22575959</ref> <ref>PMID:22895187</ref> 
[[https://www.uniprot.org/uniprot/ZNRF3_MOUSE ZNRF3_MOUSE]] 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 Frizzled and LRP6. Acts on both canonical and non-canonical Wnt signaling pathway. Acts as a tumor suppressor in the intestinal stem cell zone by inhibiting the Wnt signaling pathway, thereby resticting the size of the intestinal stem cell zone.<ref>PMID:22575959</ref> <ref>PMID:22895187</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Zinc RING finger 3 (ZNRF3) and its homolog RING finger 43 (RNF43) antagonize Wnt signaling in adult stem cells by ubiquitinating Frizzled receptors (FZD), which leads to endocytosis of the Wnt receptor. Conversely, binding of ZNRF3/RNF43 to LGR4-6 - R-spondin blocks Frizzled ubiquitination and enhances Wnt signaling. Here, we present crystal structures of the ZNRF3 ectodomain and its complex with R-spondin 1 (RSPO1). ZNRF3 binds RSPO1 and LGR5-RSPO1 with micromolar affinity via RSPO1 furin-like 1 (Fu1) domain. Anonychia-related mutations in RSPO4 support the importance of the observed interface. The ZNRF3-RSPO1 structure resembles that of LGR5-RSPO1-RNF43, though Fu2 of RSPO1 is variably oriented. The ZNRF3-binding site overlaps with trans-interactions observed in 2:2 LGR5-RSPO1 complexes, thus binding of ZNRF3/RNF43 would disrupt such an arrangement. Sequence conservation suggests a single ligand-binding site on ZNRF3, consistent with the proposed competing binding role of ZNRF3/RNF43 in Wnt signaling.
 
Structures of Wnt-Antagonist ZNRF3 and Its Complex with R-Spondin 1 and Implications for Signaling.,Peng WC, de Lau W, Madoori PK, Forneris F, Granneman JC, Clevers H, Gros P PLoS One. 2013 Dec 12;8(12):e83110. doi: 10.1371/journal.pone.0083110. PMID:24349440<ref>PMID:24349440</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4cdj" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Ubiquitin protein ligase|Ubiquitin protein ligase]]
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Mus musculus]]
[[Category: Clevers, H]]
[[Category: Clevers H]]
[[Category: Forneris, F]]
[[Category: Forneris F]]
[[Category: Granneman, J C.M]]
[[Category: Granneman JCM]]
[[Category: Gros, P]]
[[Category: Gros P]]
[[Category: Lau, W de]]
[[Category: Madoori PK]]
[[Category: Madoori, P K]]
[[Category: Peng WC]]
[[Category: Peng, W C]]
[[Category: De Lau W]]
[[Category: Adult stem cell]]
[[Category: E3 ligase]]
[[Category: Lgr5]]
[[Category: Ligase]]
[[Category: Protease-associated domain]]
[[Category: R-spondin]]
[[Category: Wnt signaling]]
[[Category: Zinc ring finger]]

Revision as of 17:40, 7 September 2022

Structure of ZNRF3 ectodomain

4cdj, resolution 1.50Å

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