View source for 4ufs


==Low resolution structure R-spondin-2 (Fu1Fu2) in complex with the ectodomains of LGR5 and ZNRF3==
<StructureSection load='4ufs' size='340' side='right'caption='[[4ufs]], [[Resolution|resolution]] 4.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ufs]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UFS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UFS FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.8&#8491;</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=4ufs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ufs OCA], [https://pdbe.org/4ufs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ufs RCSB], [https://www.ebi.ac.uk/pdbsum/4ufs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ufs ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LGR5_HUMAN LGR5_HUMAN] Orphan receptor. Stem cell marker of the intestinal epithelium and the hair follicle. Target gene of Wnt signaling.
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== Publication Abstract from PubMed ==
The four secreted R-spondin (Rspo1-4) proteins of vertebrates function as stem cell growth factors and potentiate canonical Wnt signalling. Rspo proteins act by cross-linking members of two cell surface receptor families, complexing the stem cell markers LGR4-6 with the Frizzled-specific E3 ubiquitin ligases ZNRF3/RNF43. The consequent internalisation of the ternary LGR-Rspo-E3 complex removes the E3 ligase activity, which otherwise targets the Wnt receptor Frizzled for degradation, and thus enhances Wnt signalling. Multiple combinations of LGR4-6, Rspo1-4 and ZNRF3/RNF43 are possible, implying the existence of generic interaction determinants, but also of specific differences in complex architecture and activity. We present here a high resolution crystal structure of an ectodomain variant of human LGR5 (hLGR5ecto) complexed with a signalling competent fragment of mouse Rspo2 (mRspo2Fu1-Fu2). The structure shows that the particularly potent Rspo2 ligand engages LGR5 in a fashion almost identical to that reported for hRSPO1. Comparison of our hLGR5ecto structure with previously published structures highlights a surprising plasticity of the LGR ectodomains, characterised by a nearly 9 degrees or larger rotation of the N-terminal half of the horseshoe-like fold relative to the C-terminal half. We also report a low resolution hLGR5-mRspo2Fu1-Fu2-mZNRF3ecto ternary complex structure. This crystal structure confirms our previously suggested hypothesis, showing that Rspo proteins cross-link LGRs and ZNRF3 into a 2:2:2 complex, whereas a 1:1:1 complex is formed with RNF43.

Crystal structure of R-spondin 2 in complex with the ectodomains of its receptors LGR5 and ZNRF3.,Zebisch M, Yvonne Jones E J Struct Biol. 2015 Jun 26. pii: S1047-8477(15)00137-9. doi:, 10.1016/j.jsb.2015.05.008. PMID:26123262<ref>PMID:26123262</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4ufs" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Jones EY]]
[[Category: Zebisch M]]