1th1

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[[Image:1th1.gif|left|200px]]<br /><applet load="1th1" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1th1.gif|left|200px]]
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caption="1th1, resolution 2.50&Aring;" />
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'''Beta-catenin in complex with a phosphorylated APC 20aa repeat fragment'''<br />
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{{Structure
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|PDB= 1th1 |SIZE=350|CAPTION= <scene name='initialview01'>1th1</scene>, resolution 2.50&Aring;
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|SITE=
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|LIGAND=
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|ACTIVITY=
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|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])
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}}
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'''Beta-catenin in complex with a phosphorylated APC 20aa repeat fragment'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1TH1 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=1TH1 OCA].
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1TH1 is a [[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=1TH1 OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15327769 15327769]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/15327769 15327769]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: protein-protein complex]]
[[Category: protein-protein complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:13:29 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:18:14 2008''

Revision as of 12:18, 20 March 2008


PDB ID 1th1

Drag the structure with the mouse to rotate
, resolution 2.50Å
Gene: CTNNB1, CTNNB (Homo sapiens), APC, DP2.5 (Homo sapiens)
Coordinates: save as pdb, mmCIF, xml



Beta-catenin in complex with a phosphorylated APC 20aa repeat fragment


Contents

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.

Disease

Known diseases associated with this structure: Adenoma, periampullary OMIM:[611731], Adenomatous polyposis coli OMIM:[611731], Brain tumor-polyposis syndrome 2 OMIM:[611731], Colorectal cancer OMIM:[116806], Colorectal cancer, somatic OMIM:[611731], Desmoid disease, hereditary OMIM:[611731], Gardner syndrome OMIM:[611731], Gastric cancer, somatic OMIM:[611731], Hepatoblastoma OMIM:[116806], Hepatoblastoma OMIM:[611731], Hepatocellular carcinoma OMIM:[116806], Ovarian carcinoma, endometrioid type OMIM:[116806], Pilomatricoma OMIM:[116806]

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

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