View source for 3sov


==The structure of a beta propeller domain in complex with peptide S==
<StructureSection load='3sov' size='340' side='right'caption='[[3sov]], [[Resolution|resolution]] 1.27&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3sov]] is a 2 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=3SOV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SOV FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.27&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <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=NH2:AMINO+GROUP'>NH2</scene></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=3sov FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sov OCA], [https://pdbe.org/3sov PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sov RCSB], [https://www.ebi.ac.uk/pdbsum/3sov PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sov ProSAT]</span></td></tr>
</table>
== Disease ==
[https://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.
== Function ==
[https://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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Wnt pathway inhibitors DKK1 and sclerostin (SOST) are important therapeutic targets in diseases involving bone loss or damage. It has been appreciated that Wnt coreceptors LRP5/6 are also important, as human missense mutations that result in bone overgrowth (bone mineral density, or BMD, mutations) cluster to the E1 propeller domain of LRP5. Here, we report a crystal structure of LRP6 E1 bound to an antibody, revealing that the E1 domain is a peptide recognition module. Remarkably, the consensus E1 binding sequence is a close match to a conserved tripeptide motif present in all Wnt inhibitors that bind LRP5/6. We show that this motif is important for DKK1 and SOST binding to LRP6 and for inhibitory function, providing a detailed structural explanation for the effect of the BMD mutations.

Wnt antagonists bind through a short peptide to the first beta-propeller domain of LRP5/6.,Bourhis E, Wang W, Tam C, Hwang J, Zhang Y, Spittler D, Huang OW, Gong Y, Estevez A, Zilberleyb I, Rouge L, Chiu C, Wu Y, Costa M, Hannoush RN, Franke Y, Cochran AG Structure. 2011 Oct 12;19(10):1433-42. Epub 2011 Sep 22. PMID:21944579<ref>PMID:21944579</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3sov" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bourhis E]]
[[Category: Cochran AG]]
[[Category: Franke Y]]
[[Category: Rouge L]]
[[Category: Wang W]]
[[Category: Wu Y]]
[[Category: Zhang Y]]