1jpp
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1jpp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jpp OCA], [http://www.ebi.ac.uk/pdbsum/1jpp PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1jpp RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The adenomatous polyposis coli (APC) tumor suppressor protein plays a critical role in regulating cellular levels of the oncogene product beta-catenin. APC binds to beta-catenin through a series of homologous 15 and 20 amino acid repeats. We have determined the crystal structure of a 15 amino acid beta-catenin binding repeat from APC bound to the armadillo repeat region of beta-catenin. Although it lacks significant sequence homology, the N-terminal half of the repeat binds in a manner similar to portions of E-cadherin and XTcf3, but the remaining interactions are unique to APC. We discuss the implications of this new structure for the design of therapeutics, and present evidence from structural, biochemical and sequence data, which suggest that the 20 amino acid repeats can adopt two modes of binding to beta-catenin. | The adenomatous polyposis coli (APC) tumor suppressor protein plays a critical role in regulating cellular levels of the oncogene product beta-catenin. APC binds to beta-catenin through a series of homologous 15 and 20 amino acid repeats. We have determined the crystal structure of a 15 amino acid beta-catenin binding repeat from APC bound to the armadillo repeat region of beta-catenin. Although it lacks significant sequence homology, the N-terminal half of the repeat binds in a manner similar to portions of E-cadherin and XTcf3, but the remaining interactions are unique to APC. We discuss the implications of this new structure for the design of therapeutics, and present evidence from structural, biochemical and sequence data, which suggest that the 20 amino acid repeats can adopt two modes of binding to beta-catenin. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Adenoma, periampullary OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611731 611731]], Adenomatous polyposis coli OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611731 611731]], Brain tumor-polyposis syndrome 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611731 611731]], Colorectal cancer, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611731 611731]], Desmoid disease, hereditary OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611731 611731]], Gardner syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611731 611731]], Gastric cancer, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611731 611731]], Hepatoblastoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611731 611731]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Spink, K E.]] | [[Category: Spink, K E.]] | ||
[[Category: Weis, W I.]] | [[Category: Weis, W I.]] | ||
| - | [[Category: GOL]] | ||
[[Category: anti-oncogene]] | [[Category: anti-oncogene]] | ||
[[Category: disease mutation]] | [[Category: disease mutation]] | ||
[[Category: repeat]] | [[Category: repeat]] | ||
| - | ''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 21:37:08 2008'' |
Revision as of 18:37, 30 March 2008
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| , resolution 3.10Å | |||||||
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| Ligands: | |||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
The Structure of a beta-Catenin Binding Repeat from Adenomatous Polyposis Coli (APC) in Complex with beta-Catenin
Overview
The adenomatous polyposis coli (APC) tumor suppressor protein plays a critical role in regulating cellular levels of the oncogene product beta-catenin. APC binds to beta-catenin through a series of homologous 15 and 20 amino acid repeats. We have determined the crystal structure of a 15 amino acid beta-catenin binding repeat from APC bound to the armadillo repeat region of beta-catenin. Although it lacks significant sequence homology, the N-terminal half of the repeat binds in a manner similar to portions of E-cadherin and XTcf3, but the remaining interactions are unique to APC. We discuss the implications of this new structure for the design of therapeutics, and present evidence from structural, biochemical and sequence data, which suggest that the 20 amino acid repeats can adopt two modes of binding to beta-catenin.
About this Structure
1JPP is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
Reference
Molecular mechanisms of beta-catenin recognition by adenomatous polyposis coli revealed by the structure of an APC-beta-catenin complex., Eklof Spink K, Fridman SG, Weis WI, EMBO J. 2001 Nov 15;20(22):6203-12. PMID:11707392
Page seeded by OCA on Sun Mar 30 21:37:08 2008
