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1t08
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= CTNNB1,CTNNB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), CTNNBIP1,ICAT ([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]), CTNNBIP1,ICAT ([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=1t08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t08 OCA], [http://www.ebi.ac.uk/pdbsum/1t08 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1t08 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The transcriptional coactivator beta-catenin mediates Wnt growth factor signaling. In the absence of a Wnt signal, casein kinase 1 (CK1) and glycogen synthase kinase-3beta (GSK-3beta) phosphorylate cytosolic beta-catenin, thereby flagging it for recognition and destruction by the ubiquitin/proteosome machinery. Phosphorylation occurs in a multiprotein complex that includes the kinases, beta-catenin, axin, and the Adenomatous Polyposis Coli (APC) protein. The role of APC in this process is poorly understood. CK1epsilon and GSK-3beta phosphorylate APC, which increases its affinity for beta-catenin. Crystal structures of phosphorylated and nonphosphorylated APC bound to beta-catenin reveal a phosphorylation-dependent binding motif generated by mutual priming of CK1 and GSK-3beta substrate sequences. Axin is shown to act as a scaffold for substrate phosphorylation by these kinases. Phosphorylated APC and axin bind to the same surface of, and compete directly for, beta-catenin. The structural and biochemical data suggest a novel model for how APC functions in beta-catenin degradation. | The transcriptional coactivator beta-catenin mediates Wnt growth factor signaling. In the absence of a Wnt signal, casein kinase 1 (CK1) and glycogen synthase kinase-3beta (GSK-3beta) phosphorylate cytosolic beta-catenin, thereby flagging it for recognition and destruction by the ubiquitin/proteosome machinery. Phosphorylation occurs in a multiprotein complex that includes the kinases, beta-catenin, axin, and the Adenomatous Polyposis Coli (APC) protein. The role of APC in this process is poorly understood. CK1epsilon and GSK-3beta phosphorylate APC, which increases its affinity for beta-catenin. Crystal structures of phosphorylated and nonphosphorylated APC bound to beta-catenin reveal a phosphorylation-dependent binding motif generated by mutual priming of CK1 and GSK-3beta substrate sequences. Axin is shown to act as a scaffold for substrate phosphorylation by these kinases. Phosphorylated APC and axin bind to the same surface of, and compete directly for, beta-catenin. The structural and biochemical data suggest a novel model for how APC functions in beta-catenin degradation. | ||
| - | |||
| - | ==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: Tonozuka, T.]] | [[Category: Tonozuka, T.]] | ||
[[Category: Weis, W I.]] | [[Category: Weis, W I.]] | ||
| - | [[Category: beta-catenin | + | [[Category: 20mer repeat]] |
| + | [[Category: apc]] | ||
| + | [[Category: beta-catenin]] | ||
| + | [[Category: wnt signal]] | ||
| + | [[Category: wnt signaling]] | ||
| - | ''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 23:49:20 2008'' |
Revision as of 20:49, 30 March 2008
| |||||||
| , resolution 2.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | CTNNB1,CTNNB (Homo sapiens), CTNNBIP1,ICAT (Homo sapiens), APC,DP2.5 (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of beta-catenin/ICAT helical domain/unphosphorylated APC R3
Overview
The transcriptional coactivator beta-catenin mediates Wnt growth factor signaling. In the absence of a Wnt signal, casein kinase 1 (CK1) and glycogen synthase kinase-3beta (GSK-3beta) phosphorylate cytosolic beta-catenin, thereby flagging it for recognition and destruction by the ubiquitin/proteosome machinery. Phosphorylation occurs in a multiprotein complex that includes the kinases, beta-catenin, axin, and the Adenomatous Polyposis Coli (APC) protein. The role of APC in this process is poorly understood. CK1epsilon and GSK-3beta phosphorylate APC, which increases its affinity for beta-catenin. Crystal structures of phosphorylated and nonphosphorylated APC bound to beta-catenin reveal a phosphorylation-dependent binding motif generated by mutual priming of CK1 and GSK-3beta substrate sequences. Axin is shown to act as a scaffold for substrate phosphorylation by these kinases. Phosphorylated APC and axin bind to the same surface of, and compete directly for, beta-catenin. The structural and biochemical data suggest a novel model for how APC functions in beta-catenin degradation.
About this Structure
1T08 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Mechanism of phosphorylation-dependent binding of APC to beta-catenin and its role in beta-catenin degradation., Ha NC, Tonozuka T, Stamos JL, Choi HJ, Weis WI, Mol Cell. 2004 Aug 27;15(4):511-21. PMID:15327768
Page seeded by OCA on Sun Mar 30 23:49:20 2008
