1upk

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[[Image:1upk.gif|left|200px]]<br />
 
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<applet load="1upk" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1upk, resolution 1.85&Aring;" />
 
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'''CRYSTAL STRUCTURE OF MO25 IN COMPLEX WITH A C-TERMINAL PEPTIDE OF STRAD'''<br />
 
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==Overview==
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==Crystal structure of MO25 in complex with a C-terminal peptide of STRAD==
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Mouse protein 25 alpha (MO25 alpha) is a 40-kDa protein that, together, with the STE20-related adaptor-alpha (STRAD alpha) pseudo kinase, forms a, regulatory complex capable of stimulating the activity of the LKB1 tumor, suppressor protein kinase. The latter is mutated in the inherited, Peutz-Jeghers cancer syndrome (PJS). MO25 alpha binds directly to a, conserved Trp-Glu-Phe sequence at the STRAD alpha C terminus, markedly, enhancing binding of STRAD alpha to LKB1 and increasing LKB1 catalytic, activity. The MO25 alpha crystal structure reveals a helical repeat fold, distantly related to the Armadillo proteins. A complex with the STRAD, alpha peptide reveals a hydrophobic pocket that is involved in a unique, and specific interaction with the Trp-Glu-Phe motif, further supported by, mutagenesis studies. The data represent a first step toward structural, analysis of the LKB1-STRAD-MO25 complex, and suggests that MO25 alpha is a, scaffold protein to which other regions of STRAD-LKB1, cellular LKB1, substrates or regulatory components could bind.
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<StructureSection load='1upk' size='340' side='right'caption='[[1upk]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1upk]] is a 2 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=1UPK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UPK 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]] 1.85&#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=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=1upk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1upk OCA], [https://pdbe.org/1upk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1upk RCSB], [https://www.ebi.ac.uk/pdbsum/1upk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1upk ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CAB39_HUMAN CAB39_HUMAN] Component of a complex that binds and activates STK11/LKB1. In the complex, required to stabilize the interaction between CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta) and STK11/LKB1.
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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/up/1upk_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=1upk 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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Mouse protein 25 alpha (MO25 alpha) is a 40-kDa protein that, together with the STE20-related adaptor-alpha (STRAD alpha) pseudo kinase, forms a regulatory complex capable of stimulating the activity of the LKB1 tumor suppressor protein kinase. The latter is mutated in the inherited Peutz-Jeghers cancer syndrome (PJS). MO25 alpha binds directly to a conserved Trp-Glu-Phe sequence at the STRAD alpha C terminus, markedly enhancing binding of STRAD alpha to LKB1 and increasing LKB1 catalytic activity. The MO25 alpha crystal structure reveals a helical repeat fold, distantly related to the Armadillo proteins. A complex with the STRAD alpha peptide reveals a hydrophobic pocket that is involved in a unique and specific interaction with the Trp-Glu-Phe motif, further supported by mutagenesis studies. The data represent a first step toward structural analysis of the LKB1-STRAD-MO25 complex, and suggests that MO25 alpha is a scaffold protein to which other regions of STRAD-LKB1, cellular LKB1 substrates or regulatory components could bind.
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==About this Structure==
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Crystal structure of MO25 alpha in complex with the C terminus of the pseudo kinase STE20-related adaptor.,Milburn CC, Boudeau J, Deak M, Alessi DR, van Aalten DM Nat Struct Mol Biol. 2004 Feb;11(2):193-200. Epub 2004 Jan 18. PMID:14730349<ref>PMID:14730349</ref>
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1UPK 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 MES as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UPK OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Crystal structure of MO25 alpha in complex with the C terminus of the pseudo kinase STE20-related adaptor., Milburn CC, Boudeau J, Deak M, Alessi DR, van Aalten DM, Nat Struct Mol Biol. 2004 Feb;11(2):193-200. Epub 2004 Jan 18. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14730349 14730349]
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</div>
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<div class="pdbe-citations 1upk" style="background-color:#fffaf0;"></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: Aalten, D.M.F.Van.]]
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[[Category: Alessi DR]]
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[[Category: Alessi, D.R.]]
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[[Category: Boudeau J]]
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[[Category: Boudeau, J.]]
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[[Category: Deak M]]
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[[Category: Deak, M.]]
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[[Category: Milburn CC]]
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[[Category: Milburn, C.C.]]
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[[Category: Van Aalten DMF]]
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[[Category: MES]]
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[[Category: armadillo]]
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[[Category: mo25]]
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[[Category: ste-20 related adaptor]]
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[[Category: strad]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:37:21 2007''
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Current revision

Crystal structure of MO25 in complex with a C-terminal peptide of STRAD

PDB ID 1upk

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