1luj
From Proteopedia
(New page: 200px<br /> <applet load="1luj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1luj, resolution 2.50Å" /> '''Crystal Structure o...) |
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| - | [[Image:1luj.gif|left|200px]]<br /> | + | [[Image:1luj.gif|left|200px]]<br /><applet load="1luj" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1luj" size=" | + | |
caption="1luj, resolution 2.50Å" /> | caption="1luj, resolution 2.50Å" /> | ||
'''Crystal Structure of the Beta-catenin/ICAT Complex'''<br /> | '''Crystal Structure of the Beta-catenin/ICAT Complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Beta-catenin is a multifunctional protein involved in both cell adhesion | + | Beta-catenin is a multifunctional protein involved in both cell adhesion and transcriptional activation. Transcription mediated by the beta-catenin/Tcf complex is involved in embryological development and is upregulated in various cancers. We have determined the crystal structure at 2.5 A resolution of a complex between beta-catenin and ICAT, a protein that prevents the interaction between beta-catenin and Tcf/Lef family transcription factors. ICAT contains a 3-helix bundle that binds armadillo repeats 10-12 and a C-terminal tail that, similar to Tcf and E-cadherin, binds in the groove formed by armadillo repeats 5-9 of beta-catenin. We show that ICAT selectively inhibits beta-catenin/Tcf binding in vivo, without disrupting beta-catenin/cadherin interactions. Thus, it should be possible to design cancer therapeutics that inhibit beta-catenin-mediated transcriptional activation without interfering with cell adhesion. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1LUJ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1LUJ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LUJ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Clements, W | + | [[Category: Clements, W K.]] |
| - | [[Category: Graham, T | + | [[Category: Graham, T A.]] |
[[Category: Kimelman, D.]] | [[Category: Kimelman, D.]] | ||
[[Category: Xu, W.]] | [[Category: Xu, W.]] | ||
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[[Category: wnt pathway]] | [[Category: wnt pathway]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:48:34 2008'' |
Revision as of 11:48, 21 February 2008
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Crystal Structure of the Beta-catenin/ICAT Complex
Contents |
Overview
Beta-catenin is a multifunctional protein involved in both cell adhesion and transcriptional activation. Transcription mediated by the beta-catenin/Tcf complex is involved in embryological development and is upregulated in various cancers. We have determined the crystal structure at 2.5 A resolution of a complex between beta-catenin and ICAT, a protein that prevents the interaction between beta-catenin and Tcf/Lef family transcription factors. ICAT contains a 3-helix bundle that binds armadillo repeats 10-12 and a C-terminal tail that, similar to Tcf and E-cadherin, binds in the groove formed by armadillo repeats 5-9 of beta-catenin. We show that ICAT selectively inhibits beta-catenin/Tcf binding in vivo, without disrupting beta-catenin/cadherin interactions. Thus, it should be possible to design cancer therapeutics that inhibit beta-catenin-mediated transcriptional activation without interfering with cell adhesion.
Disease
Known diseases associated with this structure: Colorectal cancer OMIM:[116806], Hepatoblastoma OMIM:[116806], Hepatocellular carcinoma OMIM:[116806], Ovarian carcinoma, endometrioid type OMIM:[116806], Pilomatricoma OMIM:[116806]
About this Structure
1LUJ is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The crystal structure of the beta-catenin/ICAT complex reveals the inhibitory mechanism of ICAT., Graham TA, Clements WK, Kimelman D, Xu W, Mol Cell. 2002 Sep;10(3):563-71. PMID:12408824
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