Extracellular architecture of an engineered canonical Wnt signaling ternary complexExtracellular architecture of an engineered canonical Wnt signaling ternary complex

Structural highlights

8ctg is a 3 chain structure with sequence from Homo sapiens, Mus musculus and Xenopus laevis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FZD8_MOUSE Receptor for Wnt proteins. Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalsomes (By similarity). The beta-catenin canonical signaling pathway leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Coreceptor along with RYK of Wnt proteins, such as WNT1.[1] [2] [3] [4]

References

  1. Sheldahl LC, Park M, Malbon CC, Moon RT. Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner. Curr Biol. 1999 Jul 1;9(13):695-8. PMID:10395542
  2. Hsieh JC, Rattner A, Smallwood PM, Nathans J. Biochemical characterization of Wnt-frizzled interactions using a soluble, biologically active vertebrate Wnt protein. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3546-51. PMID:10097073
  3. Lu W, Yamamoto V, Ortega B, Baltimore D. Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth. Cell. 2004 Oct 1;119(1):97-108. PMID:15454084 doi:10.1016/j.cell.2004.09.019
  4. Nam JS, Turcotte TJ, Smith PF, Choi S, Yoon JK. Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled 8 and LRP6 receptors and activate beta-catenin-dependent gene expression. J Biol Chem. 2006 May 12;281(19):13247-57. Epub 2006 Mar 16. PMID:16543246 doi:10.1074/jbc.M508324200

8ctg, resolution 3.80Å

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