1th1
From Proteopedia
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|PDB= 1th1 |SIZE=350|CAPTION= <scene name='initialview01'>1th1</scene>, resolution 2.50Å | |PDB= 1th1 |SIZE=350|CAPTION= <scene name='initialview01'>1th1</scene>, resolution 2.50Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= CTNNB1, CTNNB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), APC, DP2.5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= CTNNB1, CTNNB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), APC, DP2.5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1th1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1th1 OCA], [http://www.ebi.ac.uk/pdbsum/1th1 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1th1 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The tumor suppressor adenomatous polyposis coli (APC) plays a critical role in the turnover of cytosolic beta-catenin, the key effector of the canonical Wnt signaling pathway. APC contains seven 20 amino acid (20 aa) beta-catenin binding repeats that are required for beta-catenin turnover. We have determined the crystal structure of beta-catenin in complex with a phosphorylated APC fragment containing two 20 aa repeats. Surprisingly, one single phosphorylated 20 aa repeat, together with its flanking regions, covers the entire structural groove of beta-catenin and may thus compete for beta-catenin binding with all other beta-catenin armadillo repeat partners. Our biochemical studies show that phosphorylation of the APC 20 aa repeats increases the affinity of the repeats for beta-catenin by 300- to 500-fold and the phosphorylated 20 aa repeats prevent beta-catenin binding to Tcf. Our work suggests that the phosphorylation of the APC 20 aa repeats could be a critical switch for APC function. | The tumor suppressor adenomatous polyposis coli (APC) plays a critical role in the turnover of cytosolic beta-catenin, the key effector of the canonical Wnt signaling pathway. APC contains seven 20 amino acid (20 aa) beta-catenin binding repeats that are required for beta-catenin turnover. We have determined the crystal structure of beta-catenin in complex with a phosphorylated APC fragment containing two 20 aa repeats. Surprisingly, one single phosphorylated 20 aa repeat, together with its flanking regions, covers the entire structural groove of beta-catenin and may thus compete for beta-catenin binding with all other beta-catenin armadillo repeat partners. Our biochemical studies show that phosphorylation of the APC 20 aa repeats increases the affinity of the repeats for beta-catenin by 300- to 500-fold and the phosphorylated 20 aa repeats prevent beta-catenin binding to Tcf. Our work suggests that the phosphorylation of the APC 20 aa repeats could be a critical switch for APC function. | ||
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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 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=116806 116806]], 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=116806 116806]], Hepatoblastoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611731 611731]], 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]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: protein-protein complex]] | [[Category: protein-protein complex]] | ||
| - | ''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 23:55:55 2008'' |
Revision as of 20:55, 30 March 2008
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| , resolution 2.50Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | CTNNB1, CTNNB (Homo sapiens), APC, DP2.5 (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Beta-catenin in complex with a phosphorylated APC 20aa repeat fragment
Overview
The tumor suppressor adenomatous polyposis coli (APC) plays a critical role in the turnover of cytosolic beta-catenin, the key effector of the canonical Wnt signaling pathway. APC contains seven 20 amino acid (20 aa) beta-catenin binding repeats that are required for beta-catenin turnover. We have determined the crystal structure of beta-catenin in complex with a phosphorylated APC fragment containing two 20 aa repeats. Surprisingly, one single phosphorylated 20 aa repeat, together with its flanking regions, covers the entire structural groove of beta-catenin and may thus compete for beta-catenin binding with all other beta-catenin armadillo repeat partners. Our biochemical studies show that phosphorylation of the APC 20 aa repeats increases the affinity of the repeats for beta-catenin by 300- to 500-fold and the phosphorylated 20 aa repeats prevent beta-catenin binding to Tcf. Our work suggests that the phosphorylation of the APC 20 aa repeats could be a critical switch for APC function.
About this Structure
1TH1 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of a beta-catenin/APC complex reveals a critical role for APC phosphorylation in APC function., Xing Y, Clements WK, Le Trong I, Hinds TR, Stenkamp R, Kimelman D, Xu W, Mol Cell. 2004 Aug 27;15(4):523-33. PMID:15327769
Page seeded by OCA on Sun Mar 30 23:55:55 2008
