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5bq8

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Revision as of 13:27, 4 May 2017

Crystal structure of Norrin, a Wnt signalling activator, Crystal Form II

Structural highlights

5bq8 is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	4my2, 5bpu
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5bq8"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Norrin, a Wnt signalling activator, Crystal Form II==
 <StructureSection load='5bq8' size='340' side='right' caption='[[5bq8]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4my2|4my2]], [[5bpu|5bpu]]</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=5bq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bq8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5bq8 RCSB], [http://www.ebi.ac.uk/pdbsum/5bq8 PDBsum]</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=5bq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bq8 OCA], [http://pdbe.org/5bq8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bq8 RCSB], [http://www.ebi.ac.uk/pdbsum/5bq8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bq8 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 5bq8" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

5bq8

From Proteopedia

Revision as of 13:27, 4 May 2017

Crystal structure of Norrin, a Wnt signalling activator, Crystal Form II

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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