5bpq

From Proteopedia

(Difference between revisions)

Revision as of 13:30, 4 May 2017

Crystal structure of the cysteine-rich domain of human Frizzled 4 - Crystal Form II

Structural highlights

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

Disease

[FZD4_HUMAN] Retinopathy of prematurity;Familial exudative vitreoretinopathy;Persistent hyperplastic primary vitreous. The disease is caused by mutations affecting the gene represented in this entry.

Function

[FZD4_HUMAN] Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin (CTNNB1) canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin (CTNNB1) and activation of Wnt target genes. Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP). In retina, it can be both activated by Wnt protein-binding, but also by a Wnt-independent signaling via binding of norrin (NDP), promoting in both cases beta-catenin (CTNNB1) accumulation and stimulation of LEF/TCF-mediated transcriptional programs. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues.

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/5bpq"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the cysteine-rich domain of human Frizzled 4 - Crystal Form II==
 <StructureSection load='5bpq' size='340' side='right' caption='[[5bpq]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[5bpq]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BPQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BPQ FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=5bpq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5bpq RCSB], [http://www.ebi.ac.uk/pdbsum/5bpq 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=5bpq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpq OCA], [http://pdbe.org/5bpq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bpq RCSB], [http://www.ebi.ac.uk/pdbsum/5bpq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bpq ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 5bpq" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

5bpq

From Proteopedia

Revision as of 13:30, 4 May 2017

Crystal structure of the cysteine-rich domain of human Frizzled 4 - Crystal Form II

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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