1ijx
From Proteopedia
(New page: 200px<br /><applet load="1ijx" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ijx, resolution 1.9Å" /> '''CRYSTAL STRUCTURE OF ...) |
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| - | [[Image:1ijx.gif|left|200px]]<br /><applet load="1ijx" size=" | + | [[Image:1ijx.gif|left|200px]]<br /><applet load="1ijx" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ijx, resolution 1.9Å" /> | caption="1ijx, resolution 1.9Å" /> | ||
'''CRYSTAL STRUCTURE OF THE CYSTEINE-RICH DOMAIN OF SECRETED FRIZZLED-RELATED PROTEIN 3 (SFRP-3;FZB)'''<br /> | '''CRYSTAL STRUCTURE OF THE CYSTEINE-RICH DOMAIN OF SECRETED FRIZZLED-RELATED PROTEIN 3 (SFRP-3;FZB)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Members of the Frizzled family of seven-pass transmembrane proteins serve | + | 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 Structure== | ==About this Structure== | ||
| - | 1IJX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1IJX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IJX OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Dann, C | + | [[Category: Dann, C E.]] |
| - | [[Category: Hsieh, J | + | [[Category: Hsieh, J C.]] |
| - | [[Category: Leahy, D | + | [[Category: Leahy, D J.]] |
[[Category: Nathans, J.]] | [[Category: Nathans, J.]] | ||
[[Category: Rattner, A.]] | [[Category: Rattner, A.]] | ||
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[[Category: wnt receptor]] | [[Category: wnt receptor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:12:39 2008'' |
Revision as of 11:12, 21 February 2008
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CRYSTAL STRUCTURE OF THE CYSTEINE-RICH DOMAIN OF SECRETED FRIZZLED-RELATED PROTEIN 3 (SFRP-3;FZB)
Overview
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 Structure
1IJX is a Single protein structure of sequence from Mus musculus with as ligand. Full crystallographic information is available from OCA.
Reference
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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