5gje: Difference between revisions

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'''Unreleased structure'''


The entry 5gje is ON HOLD until Paper Publication
==Three-dimensional reconstruction of human LRP6 ectodomain complexed with Dkk1==
<StructureSection load='5gje' size='340' side='right' caption='[[5gje]], [[Resolution|resolution]] 21.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5gje]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GJE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GJE FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=5gje FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gje OCA], [http://pdbe.org/5gje PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gje RCSB], [http://www.ebi.ac.uk/pdbsum/5gje PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gje ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/LRP6_HUMAN LRP6_HUMAN]] Coronary artery disease - hyperlipidemia - hypertension - diabetes - osteoporosis. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/DKK1_HUMAN DKK1_HUMAN]] Idiopathic juvenile osteoporosis. 
== Function ==
[[http://www.uniprot.org/uniprot/LRP6_HUMAN LRP6_HUMAN]] Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalsomes. Cell-surface coreceptor of Wnt/beta-catenin signaling, which plays a pivotal role in bone formation. The Wnt-induced Fzd/LRP6 coreceptor complex recruits DVL1 polymers to the plasma membrane which, in turn, recruits the AXIN1/GSK3B-complex to the cell surface promoting the formation of signalsomes and inhibiting AXIN1/GSK3-mediated phosphorylation and destruction of beta-catenin. Required for posterior patterning of the epiblast during gastrulation (By similarity).<ref>PMID:11448771</ref> <ref>PMID:11357136</ref> <ref>PMID:15778503</ref> <ref>PMID:16341017</ref> <ref>PMID:16513652</ref> <ref>PMID:17400545</ref> <ref>PMID:17326769</ref> <ref>PMID:19107203</ref> <ref>PMID:19801552</ref> <ref>PMID:19293931</ref>  [[http://www.uniprot.org/uniprot/DKK1_HUMAN DKK1_HUMAN]] Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer disease.<ref>PMID:22000856</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
LDL-receptor-related protein 6 (LRP6) is a single-pass membrane glycoprotein with a large modular ectodomain and forms a higher order signaling platform upon binding Wnt ligands on the cell surface. Although multiple crystal structures are available for fragments of the LRP6 ectodomain, we lack a consensus view on the overall molecular architecture of the full-length LRP6 and its dynamic aspects. Here, we used negative-stain electron microscopy to probe conformational states of the entire ectodomain of LRP6 in solution and found that the four-module ectodomain undergoes a large bending motion hinged at the junction between the second and the third modules. Importantly, the extent of inter-domain motion is modulated by evolutionarily conserved N-glycan chains proximal to the joint. We also found that the LRP6 ectodomain becomes highly compact upon complexation with the Wnt antagonist Dkk1, suggesting a potential role for the ectodomain conformational change in the regulation of receptor oligomerization and signaling.


Authors:  
Conformational Freedom of the LRP6 Ectodomain Is Regulated by N-glycosylation and the Binding of the Wnt Antagonist Dkk1.,Matoba K, Mihara E, Tamura-Kawakami K, Miyazaki N, Maeda S, Hirai H, Thompson S, Iwasaki K, Takagi J Cell Rep. 2017 Jan 3;18(1):32-40. doi: 10.1016/j.celrep.2016.12.017. PMID:28052259<ref>PMID:28052259</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 5gje" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Hirai, H]]
[[Category: Iwasaki, K]]
[[Category: Matoba, K]]
[[Category: Mihara, E]]
[[Category: Takagi, J]]
[[Category: Tamura-Kawakami, K]]
[[Category: Thompson, S]]
[[Category: Antagonist]]
[[Category: Conformational change]]
[[Category: Dkk1]]
[[Category: Glycoprotein]]
[[Category: Lrp6]]
[[Category: Signaling protein]]
[[Category: Wnt co-receptor]]
[[Category: Wnt signaling]]
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