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3s8v

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<StructureSection load='3s8v' size='340' side='right'caption='[[3s8v]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
<StructureSection load='3s8v' size='340' side='right'caption='[[3s8v]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3s8v]] is a 3 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=3S8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S8V FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3s8v]] is a 3 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=3S8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S8V FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3s8z|3s8z]], [[3s94|3s94]]</div></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
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<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]), DKK1, UNQ492/PRO1008 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3s8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s8v OCA], [https://pdbe.org/3s8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s8v RCSB], [https://www.ebi.ac.uk/pdbsum/3s8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s8v ProSAT]</span></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=3s8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s8v OCA], [https://pdbe.org/3s8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s8v RCSB], [https://www.ebi.ac.uk/pdbsum/3s8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s8v ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[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.
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[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 ==
== Function ==
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[[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>
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Low-density-lipoprotein (LDL) receptor-related proteins 5 and 6 (LRP5/6) are Wnt co-receptors essential for Wnt/beta-catenin signaling. Dickkopf 1 (DKK1) inhibits Wnt signaling by interacting with the extracellular domains of LRP5/6 and is a drug target for multiple diseases. Here we present the crystal structures of a human LRP6-E3E4-DKK1 complex and the first and second halves of human LRP6's four propeller-epidermal growth factor (EGF) pairs (LRP6-E1E2 and LRP6-E3E4). Combined with EM analysis, these data demonstrate that LRP6-E1E2 and LRP6-E3E4 form two rigid structural blocks, with a short intervening hinge that restrains their relative orientation. The C-terminal domain of DKK1 (DKK1c) interacts with the top surface of the LRP6-E3 YWTD propeller and given their structural similarity, probably also that of the LRP6-E1 propeller, through conserved hydrophobic patches buttressed by a network of salt bridges and hydrogen bonds. Our work provides key insights for understanding LRP5/6 structure and the interaction of LRP5/6 with DKK, as well as for drug discovery.
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Crystal structures of the extracellular domain of LRP6 and its complex with DKK1.,Cheng Z, Biechele T, Wei Z, Morrone S, Moon RT, Wang L, Xu W Nat Struct Mol Biol. 2011 Oct 9. doi: 10.1038/nsmb.2139. PMID:21984209<ref>PMID:21984209</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3s8v" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Cheng, Z]]
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[[Category: Cheng Z]]
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[[Category: Xu, W]]
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[[Category: Xu W]]
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[[Category: Ldl receptor-like protein]]
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[[Category: Lrp5]]
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[[Category: Lrp6]]
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[[Category: Receptor]]
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[[Category: Signaling protein]]
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[[Category: Wnt]]
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[[Category: Ywtd b-propeller]]
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Current revision

Crystal structure of LRP6-Dkk1 complex

PDB ID 3s8v

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