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| | <StructureSection load='5bpu' size='340' side='right'caption='[[5bpu]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='5bpu' size='340' side='right'caption='[[5bpu]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5bpu]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BPU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BPU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5bpu]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BPU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BPU FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=GGL:GAMMA-L-GLUTAMIC+ACID'>GGL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GGL:GAMMA-L-GLUTAMIC+ACID'>GGL</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4my2|4my2]]</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=5bpu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpu OCA], [https://pdbe.org/5bpu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bpu RCSB], [https://www.ebi.ac.uk/pdbsum/5bpu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bpu ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NDP, EVR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5bpu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpu OCA], [http://pdbe.org/5bpu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bpu RCSB], [http://www.ebi.ac.uk/pdbsum/5bpu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bpu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/NDP_HUMAN NDP_HUMAN]] Retinopathy of prematurity;Familial exudative vitreoretinopathy;Coats disease;Persistent hyperplastic primary vitreous;Norrie disease. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/NDP_HUMAN NDP_HUMAN] Retinopathy of prematurity;Familial exudative vitreoretinopathy;Coats disease;Persistent hyperplastic primary vitreous;Norrie disease. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NDP_HUMAN NDP_HUMAN]] Activates the canonical Wnt signaling pathway through FZD4 and LRP5 coreceptor. Plays a central role in retinal vascularization by acting as a ligand for FZD4 that signals via stabilizing beta-catenin (CTNNB1) and activating LEF/TCF-mediated transcriptional programs. Acts in concert with TSPAN12 to activate FZD4 independently of the Wnt-dependent activation of FZD4, suggesting the existence of a Wnt-independent signaling that also promote accumulation the beta-catenin (CTNNB1). May be involved in a pathway that regulates neural cell differentiation and proliferation. Possible role in neuroectodermal cell-cell interaction. | + | [https://www.uniprot.org/uniprot/NDP_HUMAN NDP_HUMAN] Activates the canonical Wnt signaling pathway through FZD4 and LRP5 coreceptor. Plays a central role in retinal vascularization by acting as a ligand for FZD4 that signals via stabilizing beta-catenin (CTNNB1) and activating LEF/TCF-mediated transcriptional programs. Acts in concert with TSPAN12 to activate FZD4 independently of the Wnt-dependent activation of FZD4, suggesting the existence of a Wnt-independent signaling that also promote accumulation the beta-catenin (CTNNB1). May be involved in a pathway that regulates neural cell differentiation and proliferation. Possible role in neuroectodermal cell-cell interaction. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chang, T H]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Harlos, K]] | + | [[Category: Chang T-H]] |
| - | [[Category: Hsieh, F L]] | + | [[Category: Harlos K]] |
| - | [[Category: Jones, E Y]] | + | [[Category: Hsieh F-L]] |
| - | [[Category: Cystine-knot like growth factor]]
| + | [[Category: Jones EY]] |
| - | [[Category: Ligand for frizzled 4 receptor]]
| + | |
| - | [[Category: Norrie disease protein]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Wnt signalling pathway]]
| + | |
| Structural highlights
Disease
NDP_HUMAN Retinopathy of prematurity;Familial exudative vitreoretinopathy;Coats disease;Persistent hyperplastic primary vitreous;Norrie disease. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
NDP_HUMAN Activates the canonical Wnt signaling pathway through FZD4 and LRP5 coreceptor. Plays a central role in retinal vascularization by acting as a ligand for FZD4 that signals via stabilizing beta-catenin (CTNNB1) and activating LEF/TCF-mediated transcriptional programs. Acts in concert with TSPAN12 to activate FZD4 independently of the Wnt-dependent activation of FZD4, suggesting the existence of a Wnt-independent signaling that also promote accumulation the beta-catenin (CTNNB1). May be involved in a pathway that regulates neural cell differentiation and proliferation. Possible role in neuroectodermal cell-cell interaction.
Publication Abstract from PubMed
Wnt signalling regulates multiple processes including angiogenesis, inflammation, and tumorigenesis. Norrin (Norrie Disease Protein) is a cystine-knot like growth factor. Although unrelated to Wnt, Norrin activates the Wnt/beta-catenin pathway. Signal complex formation involves Frizzled4 (Fz4), low-density lipoprotein receptor related protein 5/6 (Lrp5/6), Tetraspanin-12 and glycosaminoglycans (GAGs). Here, we report crystallographic and small-angle X-ray scattering analyses of Norrin in complex with Fz4 cysteine-rich domain (Fz4CRD), of this complex bound with GAG analogues, and of unliganded Norrin and Fz4CRD. Our structural, biophysical and cellular data, map Fz4 and putative Lrp5/6 binding sites to distinct patches on Norrin, and reveal a GAG binding site spanning Norrin and Fz4CRD. These results explain numerous disease-associated mutations. Comparison with the Xenopus Wnt8-mouse Fz8CRD complex reveals Norrin mimics Wnt for Frizzled recognition. The production and characterization of wild-type and mutant Norrins reported here open new avenues for the development of therapeutics to combat abnormal Norrin/Wnt signalling.
Structure and functional properties of Norrin mimic Wnt for signalling with Frizzled4, Lrp5/6, and proteoglycan.,Chang TH, Hsieh FL, Zebisch M, Harlos K, Elegheert J, Jones EY Elife. 2015 Jul 9;4. doi: 10.7554/eLife.06554. PMID:26158506[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chang TH, Hsieh FL, Zebisch M, Harlos K, Elegheert J, Jones EY. Structure and functional properties of Norrin mimic Wnt for signalling with Frizzled4, Lrp5/6, and proteoglycan. Elife. 2015 Jul 9;4. doi: 10.7554/eLife.06554. PMID:26158506 doi:http://dx.doi.org/10.7554/eLife.06554
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