1p22

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[[Image:1p22.png|left|200px]]
 
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==Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity on the SCFbeta-TrCP1 ubiquitin ligase==
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The line below this paragraph, containing "STRUCTURE_1p22", creates the "Structure Box" on the page.
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<StructureSection load='1p22' size='340' side='right'caption='[[1p22]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1p22]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P22 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1P22 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]] 2.95&#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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{{STRUCTURE_1p22| PDB=1p22 | SCENE= }}
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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=1p22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p22 OCA], [https://pdbe.org/1p22 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p22 RCSB], [https://www.ebi.ac.uk/pdbsum/1p22 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p22 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/FBW1A_HUMAN FBW1A_HUMAN] Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes and binds to phosphorylated target proteins. SCF(BTRC) mediates the ubiquitination of CTNNB1 and participates in Wnt signaling. SCF(BTRC) mediates the ubiquitination of NFKBIA, NFKBIB and NFKBIE; the degradation frees the associated NFKB1 to translocate into the nucleus and to activate transcription. Ubiquitination of NFKBIA occurs at 'Lys-21' and 'Lys-22'. SCF(BTRC) mediates the ubiquitination of phosphorylated NFKB1/nuclear factor NF-kappa-B p105 subunit, ATF4, SMAD3, SMAD4, CDC25A, DLG1, FBXO5 and probably NFKB2. SCF(BTRC) mediates the ubiquitination of phosphorylated SNAI1. May be involved in ubiquitination and subsequent proteasomal degradation through a DBB1-CUL4 E3 ubiquitin-protein ligase. Required for activation of NFKB-mediated transcription by IL1B, MAP3K14, MAP3K1, IKBKB and TNF. Required for proteolytic processing of GLI3.<ref>PMID:9859996</ref> <ref>PMID:10066435</ref> <ref>PMID:10497169</ref> <ref>PMID:10835356</ref> <ref>PMID:10644755</ref> <ref>PMID:11359933</ref> <ref>PMID:11238952</ref> <ref>PMID:11994270</ref> <ref>PMID:12791267</ref> <ref>PMID:14681206</ref> <ref>PMID:12902344</ref> <ref>PMID:14603323</ref> <ref>PMID:14988407</ref> <ref>PMID:15448698</ref> <ref>PMID:16371461</ref>
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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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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p2/1p22_consurf.spt"</scriptWhenChecked>
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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=1p22 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 SCF ubiquitin ligases catalyze protein ubiquitination in diverse cellular processes. SCFs bind substrates through the interchangeable F box protein subunit, with the &gt;70 human F box proteins allowing the recognition of a wide range of substrates. The F box protein beta-TrCP1 recognizes the doubly phosphorylated DpSGphiXpS destruction motif, present in beta-catenin and IkappaB, and directs the SCF(beta-TrCP1) to ubiquitinate these proteins at specific lysines. The 3.0 A structure of a beta-TrCP1-Skp1-beta-catenin complex reveals the basis of substrate recognition by the beta-TrCP1 WD40 domain. The structure, together with the previous SCF(Skp2) structure, leads to the model of SCF catalyzing ubiquitination by increasing the effective concentration of the substrate lysine at the E2 active site. The model's prediction that the lysine-destruction motif spacing is a determinant of ubiquitination efficiency is confirmed by measuring ubiquitination rates of mutant beta-catenin peptides, solidifying the model and also providing a mechanistic basis for lysine selection.
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===Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity on the SCFbeta-TrCP1 ubiquitin ligase===
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Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin ligase.,Wu G, Xu G, Schulman BA, Jeffrey PD, Harper JW, Pavletich NP Mol Cell. 2003 Jun;11(6):1445-56. PMID:12820959<ref>PMID:12820959</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1p22" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 12820959 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12820959}}
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==About this Structure==
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[[1p22]] is a 3 chain structure of [[Catenin]] with sequence 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=1P22 OCA].
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==See Also==
==See Also==
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*[[Catenin]]
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*[[Catenin 3D structures|Catenin 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:12820959</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Harper, J W.]]
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[[Category: Large Structures]]
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[[Category: Jeffrey, P D.]]
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[[Category: Harper JW]]
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[[Category: Pavletich, N P.]]
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[[Category: Jeffrey PD]]
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[[Category: Schulman, B A.]]
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[[Category: Pavletich NP]]
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[[Category: Wu, G.]]
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[[Category: Schulman BA]]
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[[Category: Xu, G.]]
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[[Category: Wu G]]
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[[Category: Degradation]]
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[[Category: Xu G]]
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[[Category: Signaling protein]]
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[[Category: Ubiquitination]]
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Current revision

Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity on the SCFbeta-TrCP1 ubiquitin ligase

PDB ID 1p22

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