1jpw
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2bct|2bct]], [[3bct|3bct]], [[1g3j|1G3J]], [[1i7w|1I7W]], [[1i7x|1I7X]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1jpw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jpw OCA], [http://www.ebi.ac.uk/pdbsum/1jpw PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1jpw RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The multifunctional protein beta-catenin is important for cell adhesion, because it binds cadherins, and the Wnt signal transduction pathway, where it interacts with the Adenomatous polyposis coli (APC) protein and TCF/Lef family transcription factors. Mutations in APC or in beta-catenin are estimated to trigger formation of over 90% of all colon cancers. In colonic epithelia, these mutations produce elevated levels of Tcf4-beta-catenin, which stimulates a transcriptional response that initiates polyp formation and eventually malignant growth. Thus, disruption of the Tcf4-beta-catenin interaction may be an attractive goal for therapeutic intervention. Here we describe the crystal structure of a human Tcf4-beta-catenin complex and compare it with recent structures of beta-catenin in complex with Xenopus Tcf3 (XTcf3) and mammalian E-cadherin. The structure reveals anticipated similarities with the closely related XTcf3 complex but unexpectedly lacks one component observed in the XTcf3 structure. | The multifunctional protein beta-catenin is important for cell adhesion, because it binds cadherins, and the Wnt signal transduction pathway, where it interacts with the Adenomatous polyposis coli (APC) protein and TCF/Lef family transcription factors. Mutations in APC or in beta-catenin are estimated to trigger formation of over 90% of all colon cancers. In colonic epithelia, these mutations produce elevated levels of Tcf4-beta-catenin, which stimulates a transcriptional response that initiates polyp formation and eventually malignant growth. Thus, disruption of the Tcf4-beta-catenin interaction may be an attractive goal for therapeutic intervention. Here we describe the crystal structure of a human Tcf4-beta-catenin complex and compare it with recent structures of beta-catenin in complex with Xenopus Tcf3 (XTcf3) and mammalian E-cadherin. The structure reveals anticipated similarities with the closely related XTcf3 complex but unexpectedly lacks one component observed in the XTcf3 structure. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Colorectal cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=116806 116806]], Diabetes mellitus, type 2, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602228 602228]], Hepatoblastoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=116806 116806]], Hepatocellular carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=116806 116806]], Ovarian carcinoma, endometrioid type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=116806 116806]], Pilomatricoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=116806 116806]], Pitt-Hopkins syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602272 602272]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: transcription factor]] | [[Category: transcription factor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:37:15 2008'' |
Revision as of 18:37, 30 March 2008
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| , resolution 2.5Å | |||||||
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| Related: | 2bct, 3bct, 1G3J, 1I7W, 1I7X
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of a Human Tcf-4 / beta-Catenin Complex
Overview
The multifunctional protein beta-catenin is important for cell adhesion, because it binds cadherins, and the Wnt signal transduction pathway, where it interacts with the Adenomatous polyposis coli (APC) protein and TCF/Lef family transcription factors. Mutations in APC or in beta-catenin are estimated to trigger formation of over 90% of all colon cancers. In colonic epithelia, these mutations produce elevated levels of Tcf4-beta-catenin, which stimulates a transcriptional response that initiates polyp formation and eventually malignant growth. Thus, disruption of the Tcf4-beta-catenin interaction may be an attractive goal for therapeutic intervention. Here we describe the crystal structure of a human Tcf4-beta-catenin complex and compare it with recent structures of beta-catenin in complex with Xenopus Tcf3 (XTcf3) and mammalian E-cadherin. The structure reveals anticipated similarities with the closely related XTcf3 complex but unexpectedly lacks one component observed in the XTcf3 structure.
About this Structure
1JPW is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of a human Tcf4-beta-catenin complex., Poy F, Lepourcelet M, Shivdasani RA, Eck MJ, Nat Struct Biol. 2001 Dec;8(12):1053-7. PMID:11713476
Page seeded by OCA on Sun Mar 30 21:37:15 2008
