1v18

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(New page: 200px<br /> <applet load="1v18" size="450" color="white" frame="true" align="right" spinBox="true" caption="1v18, resolution 2.1&Aring;" /> '''THE CRYSTAL STRUCTUR...)
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[[Image:1v18.gif|left|200px]]<br />
 
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<applet load="1v18" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1v18, resolution 2.1&Aring;" />
 
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'''THE CRYSTAL STRUCTURE OF BETA-CATENIN ARMADILLO REPEAT COMPLEXED WITH A PHOSPHORYLATED APC 20MER REPEAT.'''<br />
 
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==Overview==
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==The crystal structure of beta-catenin armadillo repeat complexed with a phosphorylated APC 20mer repeat.==
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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.
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<StructureSection load='1v18' size='340' side='right'caption='[[1v18]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1v18]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V18 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1V18 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1v18 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1v18 OCA], [https://pdbe.org/1v18 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1v18 RCSB], [https://www.ebi.ac.uk/pdbsum/1v18 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1v18 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CTNB1_MOUSE CTNB1_MOUSE] Key downstream component of the canonical Wnt signaling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Involved in the regulation of cell adhesion. Acts as a negative regulator of centrosome cohesion. Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization. Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 (By similarity).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v1/1v18_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1v18 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==Disease==
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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<ref>PMID:15327768</ref>
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Known diseases associated with this structure: Adenoma, periampullary OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=175100 175100]], Adenomatous polyposis coli OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=175100 175100]], Adenomatous polyposis coli, attenuated OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=175100 175100]], Colorectal cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=175100 175100]], Desmoid disease, hereditary OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=175100 175100]], Gardner syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=175100 175100]], Gastric cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=175100 175100]], Turcot syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=175100 175100]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1V18 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1V18 OCA].
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</div>
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<div class="pdbe-citations 1v18" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15327768 15327768]
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*[[Catenin 3D structures|Catenin 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Protein complex]]
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[[Category: Ha N-C]]
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[[Category: Ha, N.C.]]
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[[Category: Weis WI]]
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[[Category: Weis, W.I.]]
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[[Category: beta-catenin degradation complex]]
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[[Category: cell adhesion]]
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[[Category: transcription]]
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[[Category: transcription regulation]]
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[[Category: wnt signal]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:40:47 2007''
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Current revision

The crystal structure of beta-catenin armadillo repeat complexed with a phosphorylated APC 20mer repeat.

PDB ID 1v18

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