2ovr

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(New page: 200px<br /> <applet load="2ovr" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ovr, resolution 2.50&Aring;" /> '''Structure of the Sk...)
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[[Image:2ovr.gif|left|200px]]<br />
 
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<applet load="2ovr" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2ovr, resolution 2.50&Aring;" />
 
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'''Structure of the Skp1-Fbw7-CyclinEdegN complex'''<br />
 
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==Overview==
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==Structure of the Skp1-Fbw7-CyclinEdegN complex==
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The ubiquitin-mediated proteolysis of cyclin E plays a central role in, cell-cycle progression, and cyclin E accumulation is a common event in, cancer. Cyclin E degradation is triggered by multisite phosphorylation, which induces binding to the SCF(Fbw7) ubiquitin ligase complex., Structures of the Skp1-Fbw7 complex bound to cyclin E peptides identify a, doubly phosphorylated pThr380/pSer384 cyclin E motif as an optimal, high-affinity degron and a singly phosphorylated pThr62 motif as a, low-affinity one. Biochemical data indicate that the closely related yeast, SCF(Cdc4) complex recognizes the multisite phosphorylated Sic1 substrate, similarly and identify three doubly phosphorylated Sic1 degrons, each, capable of high-affinity interactions with two Cdc4 phosphate binding, sites. A model that explains the role of multiple cyclin E/Sic1 degrons is, provided by the findings that Fbw7 and Cdc4 dimerize, that Fbw7, dimerization enhances the turnover of a weakly associated cyclin E in, vivo, and that Cdc4 dimerization increases the rate and processivity of, Sic1 ubiquitination in vitro.
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<StructureSection load='2ovr' size='340' side='right'caption='[[2ovr]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[2ovr]] 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=2OVR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OVR FirstGlance]. <br>
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2OVR is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2OVR OCA].
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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]] 2.5&#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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
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==Reference==
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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=2ovr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ovr OCA], [https://pdbe.org/2ovr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ovr RCSB], [https://www.ebi.ac.uk/pdbsum/2ovr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ovr ProSAT]</span></td></tr>
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Structure of a Fbw7-Skp1-Cyclin E Complex: Multisite-Phosphorylated Substrate Recognition by SCF Ubiquitin Ligases., Hao B, Oehlmann S, Sowa ME, Harper JW, Pavletich NP, Mol Cell. 2007 Apr 13;26(1):131-43. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17434132 17434132]
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SKP1_HUMAN SKP1_HUMAN] Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(Cyclin F) directs ubiquitination of CP110.<ref>PMID:16209941</ref> <ref>PMID:20181953</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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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ov/2ovr_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2ovr ConSurf].
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<div style="clear:both"></div>
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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: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Hao, B.]]
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[[Category: Hao B]]
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[[Category: Harper, J.W.]]
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[[Category: Harper JW]]
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[[Category: Oehlmann, S.]]
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[[Category: Oehlmann S]]
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[[Category: Pavletich, N.P.]]
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[[Category: Pavletich NP]]
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[[Category: Sowa, M.E.]]
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[[Category: Sowa ME]]
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[[Category: SO4]]
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[[Category: f-box; wd40 domains; double phosphorylation]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:17:14 2007''
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Current revision

Structure of the Skp1-Fbw7-CyclinEdegN complex

PDB ID 2ovr

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