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3soq
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| - | [[Image:3soq.jpg|left|200px]] | ||
| - | < | + | ==The structure of the first YWTD beta propeller domain of LRP6 in complex with a DKK1 peptide== |
| - | + | <StructureSection load='3soq' size='340' side='right'caption='[[3soq]], [[Resolution|resolution]] 1.90Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[3soq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SOQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SOQ FirstGlance]. <br> | |
| - | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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></td></tr> | |
| - | - | + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> |
| - | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3sob|3sob]], [[3sov|3sov]]</div></td></tr> | |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LRP6 ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3soq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3soq OCA], [https://pdbe.org/3soq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3soq RCSB], [https://www.ebi.ac.uk/pdbsum/3soq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3soq 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. [[https://www.uniprot.org/uniprot/DKK1_HUMAN DKK1_HUMAN]] Idiopathic juvenile osteoporosis. | ||
| + | == 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> [[https://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 == | ||
| + | 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | == | + | </div> |
| - | + | <div class="pdbe-citations 3soq" style="background-color:#fffaf0;"></div> | |
| - | [[Category: | + | == References == |
| - | [[Category: Bourhis, E | + | <references/> |
| - | [[Category: Cochran, A G | + | __TOC__ |
| - | [[Category: Franke, Y | + | </StructureSection> |
| - | [[Category: Rouge, L | + | [[Category: Human]] |
| - | [[Category: Wang, W | + | [[Category: Large Structures]] |
| - | [[Category: Wu, Y | + | [[Category: Bourhis, E]] |
| - | [[Category: Zhang, Y | + | [[Category: Cochran, A G]] |
| + | [[Category: Franke, Y]] | ||
| + | [[Category: Rouge, L]] | ||
| + | [[Category: Wang, W]] | ||
| + | [[Category: Wu, Y]] | ||
| + | [[Category: Zhang, Y]] | ||
[[Category: Beta propeller]] | [[Category: Beta propeller]] | ||
[[Category: Protein binding-antagonist complex]] | [[Category: Protein binding-antagonist complex]] | ||
Current revision
The structure of the first YWTD beta propeller domain of LRP6 in complex with a DKK1 peptide
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