5fww

From Proteopedia

(Difference between revisions)

Revision as of 15:33, 26 July 2016

Wnt modulator Kremen in complex with DKK1 (CRD2) and LRP6 (PE3PE4)

Structural highlights

5fww is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	5fws, 5fwt, 5fwu, 5fwv
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[LRP6_HUMAN] Coronary artery disease - hyperlipidemia - hypertension - diabetes - osteoporosis. The disease is caused by mutations affecting the gene represented in this entry. [DKK1_HUMAN] Idiopathic juvenile osteoporosis.

Function

[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).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] [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.^[11] [KREM1_HUMAN] Receptor for Dickkopf protein. Cooperates with Dickkopf to block Wnt/beta-catenin signaling (By similarity).

References

↑ Semenov MV, Tamai K, Brott BK, Kuhl M, Sokol S, He X. Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Curr Biol. 2001 Jun 26;11(12):951-61. PMID:11448771
↑ Mao B, Wu W, Li Y, Hoppe D, Stannek P, Glinka A, Niehrs C. LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature. 2001 May 17;411(6835):321-5. PMID:11357136 doi:10.1038/35077108
↑ Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE, Wu D. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 2005 May 20;280(20):19883-7. Epub 2005 Mar 18. PMID:15778503 doi:10.1074/jbc.M413274200
↑ Zeng X, Tamai K, Doble B, Li S, Huang H, Habas R, Okamura H, Woodgett J, He X. A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation. Nature. 2005 Dec 8;438(7069):873-7. PMID:16341017 doi:10.1038/nature04185
↑ Swiatek W, Kang H, Garcia BA, Shabanowitz J, Coombs GS, Hunt DF, Virshup DM. Negative regulation of LRP6 function by casein kinase I epsilon phosphorylation. J Biol Chem. 2006 May 5;281(18):12233-41. Epub 2006 Mar 2. PMID:16513652 doi:10.1074/jbc.M510580200
↑ Wei Q, Yokota C, Semenov MV, Doble B, Woodgett J, He X. R-spondin1 is a high affinity ligand for LRP6 and induces LRP6 phosphorylation and beta-catenin signaling. J Biol Chem. 2007 May 25;282(21):15903-11. Epub 2007 Mar 30. PMID:17400545 doi:10.1074/jbc.M701927200
↑ Mi K, Johnson GV. Regulated proteolytic processing of LRP6 results in release of its intracellular domain. J Neurochem. 2007 Apr;101(2):517-29. Epub 2007 Feb 26. PMID:17326769 doi:10.1111/j.1471-4159.2007.04447.x
↑ Piao S, Lee SH, Kim H, Yum S, Stamos JL, Xu Y, Lee SJ, Lee J, Oh S, Han JK, Park BJ, Weis WI, Ha NC. Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling. PLoS One. 2008;3(12):e4046. doi: 10.1371/journal.pone.0004046. Epub 2008 Dec 24. PMID:19107203 doi:10.1371/journal.pone.0004046
↑ Chen M, Philipp M, Wang J, Premont RT, Garrison TR, Caron MG, Lefkowitz RJ, Chen W. G Protein-coupled receptor kinases phosphorylate LRP6 in the Wnt pathway. J Biol Chem. 2009 Dec 11;284(50):35040-8. doi: 10.1074/jbc.M109.047456. Epub 2009, Oct 2. PMID:19801552 doi:10.1074/jbc.M109.047456
↑ Wu G, Huang H, Garcia Abreu J, He X. Inhibition of GSK3 phosphorylation of beta-catenin via phosphorylated PPPSPXS motifs of Wnt coreceptor LRP6. PLoS One. 2009;4(3):e4926. doi: 10.1371/journal.pone.0004926. Epub 2009 Mar 18. PMID:19293931 doi:10.1371/journal.pone.0004926
↑ Ahn VE, Chu ML, Choi HJ, Tran D, Abo A, Weis WI. Structural Basis of Wnt Signaling Inhibition by Dickkopf Binding to LRP5/6. Dev Cell. 2011 Oct 12. PMID:22000856 doi:10.1016/j.devcel.2011.09.003

1 Structural highlights
2 Disease
3 Function
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5fww"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5fww is ON HOLD
+==Wnt modulator Kremen in complex with DKK1 (CRD2) and LRP6 (PE3PE4)==
+<StructureSection load='5fww' size='340' side='right' caption='[[5fww]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
-Authors: Zebisch, M., Jackson, V.A., Jones, E.Y.
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5fww]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FWW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FWW FirstGlance]. <br>
-Description: Wnt signalling ternary complex
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
-[[Category: Unreleased Structures]]
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fws|5fws]], [[5fwt|5fwt]], [[5fwu|5fwu]], [[5fwv|5fwv]]</td></tr>
-[[Category: Jackson, V.A]]
+<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=5fww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fww OCA], [http://pdbe.org/5fww PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fww RCSB], [http://www.ebi.ac.uk/pdbsum/5fww PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fww 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>  [[http://www.uniprot.org/uniprot/KREM1_HUMAN KREM1_HUMAN]] Receptor for Dickkopf protein. Cooperates with Dickkopf to block Wnt/beta-catenin signaling (By similarity).
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Jackson, V A]]
+[[Category: Jones, E Y]]
 [[Category: Zebisch, M]]
-[[Category: Jones, E.Y]]
+[[Category: Cell surface]]
+[[Category: Membrane protein]]
+[[Category: Signaling protein]]
+[[Category: Signalling]]
+[[Category: Wnt]]

5fww

From Proteopedia

Revision as of 15:33, 26 July 2016

Wnt modulator Kremen in complex with DKK1 (CRD2) and LRP6 (PE3PE4)

Structural highlights

Disease

Function

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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