1ijx
CRYSTAL STRUCTURE OF THE CYSTEINE-RICH DOMAIN OF SECRETED FRIZZLED-RELATED PROTEIN 3 (SFRP-3;FZB)
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OverviewOverview
Members of the Frizzled family of seven-pass transmembrane proteins serve, as receptors for Wnt signalling proteins. Wnt proteins have important, roles in the differentiation and patterning of diverse tissues during, animal development, and inappropriate activation of Wnt signalling, pathways is a key feature of many cancers. An extracellular cysteine-rich, domain (CRD) at the amino terminus of Frizzled proteins binds Wnt, proteins, as do homologous domains in soluble proteins-termed secreted, Frizzled-related proteins-that function as antagonists of Wnt signalling., Recently, an LDL-receptor-related protein has been shown to function as a, co-receptor for Wnt proteins and to bind to a Frizzled CRD in a, Wnt-dependent manner. To investigate the molecular nature of the Wnt, signalling complex, we determined the crystal structures of the CRDs from, mouse Frizzled 8 and secreted Frizzled-related protein 3. Here we show a, previously unknown protein fold, and the design and interpretation of CRD, mutations that identify a Wnt-binding site. CRDs exhibit a conserved dimer, interface that may be a feature of Wnt signalling. This work provides a, framework for studies of homologous CRDs in proteins including, muscle-specific kinase and Smoothened, a component of the Hedgehog, signalling pathway.
About this StructureAbout this Structure
1IJX is a Single protein structure of sequence from Mus musculus with SO4 as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains., Dann CE, Hsieh JC, Rattner A, Sharma D, Nathans J, Leahy DJ, Nature. 2001 Jul 5;412(6842):86-90. PMID:11452312
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