4kng

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{{STRUCTURE_4kng| PDB=4kng | SCENE= }}
 
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===Crystal structure of human LGR5-RSPO1-RNF43===
 
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{{ABSTRACT_PUBMED_23756651}}
 
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==Disease==
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==Crystal structure of human LGR5-RSPO1-RNF43==
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[[http://www.uniprot.org/uniprot/RSPO1_HUMAN RSPO1_HUMAN]] Palmoplantar keratoderma - XX sex reversal - predisposition to squamous cell carcinoma. Keratoderma, palmoplantar, with squamous cell carcinoma of skin and sex reversal (PKKSCC) [MIM:[http://omim.org/entry/610644 610644]]: A recessive syndrome characterized by XX (female to male) SRY-independent sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin. Note=The disease is caused by mutations affecting the gene represented in this entry.
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<StructureSection load='4kng' size='340' side='right'caption='[[4kng]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4kng]] is a 6 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=4KNG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KNG FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4kng FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kng OCA], [https://pdbe.org/4kng PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kng RCSB], [https://www.ebi.ac.uk/pdbsum/4kng PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kng ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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R-spondins (RSPOs) enhance Wnt signaling, affect stem cell behavior, bind to leucine-rich repeat-containing G-protein-coupled receptors 4-6, (LGR4-6) and the transmembrane E3 ubiquitin ligases RING finger 43/zinc and RING finger 3 (RNF43/ZNRF3). The structure of RSPO1 bound to both LGR5 and RNF43 ectodomains confirms their physical linkage. RSPO1 is sandwiched by LGR5 and RNF43, with its rod module of the cysteine-rich domain (CRD) contacting LGR5 and a hairpin inserted into RNF43. LGR5 does not contact RNF43 but increases the affinity of RSPO1 to RNF43, supporting LGR5 as an engagement receptor and RNF43 as an effector receptor. Disease mutations map to the RSPO1-RNF43 interface, which promises therapeutic targeting.
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==Function==
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The structural basis of R-spondin recognition by LGR5 and RNF43.,Chen PH, Chen X, Lin Z, Fang D, He X Genes Dev. 2013 Jun 11. PMID:23756651<ref>PMID:23756651</ref>
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[[http://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. [[http://www.uniprot.org/uniprot/RNF43_HUMAN RNF43_HUMAN]] E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination, endocytosis and subsequent degradation of Wnt receptor complex components Frizzled. 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:18313049</ref> <ref>PMID:22575959</ref> <ref>PMID:22895187</ref> [[http://www.uniprot.org/uniprot/RSPO1_HUMAN RSPO1_HUMAN]] Activator of the beta-catenin signaling cascade, leading to TCF-dependent gene activation. Acts both in the canonical Wnt/beta-catenin-dependent pathway and in non-canonical Wnt signaling pathway, probably by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway. Has a essential roles in ovary determination.<ref>PMID:16109882</ref> <ref>PMID:22575959</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4kng]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KNG OCA].
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</div>
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<div class="pdbe-citations 4kng" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:023756651</ref><references group="xtra"/><references/>
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*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Chen, P H.]]
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[[Category: Large Structures]]
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[[Category: He, X.]]
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[[Category: Chen PH]]
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[[Category: Cysteine-rich domain]]
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[[Category: He X]]
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[[Category: Furin-repeat]]
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[[Category: Leucine-rich repeat]]
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[[Category: Ligand recognition]]
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[[Category: Membrane protein]]
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[[Category: N-linked glycosylation]]
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[[Category: Protease-associated domain]]
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[[Category: Protein-protein interaction]]
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[[Category: Signaling protein]]
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Current revision

Crystal structure of human LGR5-RSPO1-RNF43

PDB ID 4kng

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