1kbe

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(New page: 200px<br /><applet load="1kbe" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kbe" /> '''Solution structure of the cysteine-rich C1 d...)
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[[Image:1kbe.jpg|left|200px]]<br /><applet load="1kbe" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1kbe" />
 
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'''Solution structure of the cysteine-rich C1 domain of Kinase Suppressor of Ras'''<br />
 
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==Overview==
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==Solution structure of the cysteine-rich C1 domain of Kinase Suppressor of Ras==
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Kinase suppressor of Ras (KSR) is a conserved component of the Ras pathway, that acts as a molecular scaffold to promote signal transmission from, Raf-1 to MEK and MAPK. All KSR proteins contain a conserved cysteine-rich, C1 domain, and studies have implicated this domain in the regulation of, KSR1 subcellular localization and function. To further elucidate the, biological role of the KSR1 C1 domain, we have determined its, three-dimensional solution structure using nuclear magnetic resonance, (NMR). We find that while the overall topology of the KSR1 C1 domain is, similar to the C1 domains of Raf-1 and PKCgamma, the predicted, ligand-binding region and the surface charge distribution are unique., Moreover, by generating chimeric proteins in which these domains have been, swapped, we find that the C1 domains of Raf-1, PKCgamma, and KSR1 are not, functionally interchangeable. The KSR1 C1 domain does not bind with high, affinity or respond biologically to phorbol esters or ceramide, and it, does not interact directly with Ras, indicating that the putative, ligand(s) for the KSR1 C1 domain are distinct from those that interact, with PKCgamma and Raf-1. In addition, our analysis of the chimeric, proteins supports the model that Raf-1 is a ceramide-activated kinase and, that its C1 domain is involved in the ceramide-mediated response. Finally, our findings demonstrate an absolute requirement of the KSR1 C1 domain in, mediating the membrane localization of KSR1, a crucial feature of its, scaffolding activity. Together, these results underscore the functional, specificity of these important regulatory domains and demonstrate that the, structural features of the C1 domains can provide valuable insight into, their ligand-binding properties.
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<StructureSection load='1kbe' size='340' side='right'caption='[[1kbe]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1kbe]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KBE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KBE 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">Solution NMR, 1 model</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=ZN:ZINC+ION'>ZN</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=1kbe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kbe OCA], [https://pdbe.org/1kbe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kbe RCSB], [https://www.ebi.ac.uk/pdbsum/1kbe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kbe ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/KSR1_MOUSE KSR1_MOUSE] Location-regulated scaffolding protein connecting MEK to RAF. Promotes MEK and RAF phosphorylation and activity through assembly of an activated signaling complex. By itself, it has no demonstrated kinase activity.
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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/kb/1kbe_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=1kbe 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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Kinase suppressor of Ras (KSR) is a conserved component of the Ras pathway that acts as a molecular scaffold to promote signal transmission from Raf-1 to MEK and MAPK. All KSR proteins contain a conserved cysteine-rich C1 domain, and studies have implicated this domain in the regulation of KSR1 subcellular localization and function. To further elucidate the biological role of the KSR1 C1 domain, we have determined its three-dimensional solution structure using nuclear magnetic resonance (NMR). We find that while the overall topology of the KSR1 C1 domain is similar to the C1 domains of Raf-1 and PKCgamma, the predicted ligand-binding region and the surface charge distribution are unique. Moreover, by generating chimeric proteins in which these domains have been swapped, we find that the C1 domains of Raf-1, PKCgamma, and KSR1 are not functionally interchangeable. The KSR1 C1 domain does not bind with high affinity or respond biologically to phorbol esters or ceramide, and it does not interact directly with Ras, indicating that the putative ligand(s) for the KSR1 C1 domain are distinct from those that interact with PKCgamma and Raf-1. In addition, our analysis of the chimeric proteins supports the model that Raf-1 is a ceramide-activated kinase and that its C1 domain is involved in the ceramide-mediated response. Finally, our findings demonstrate an absolute requirement of the KSR1 C1 domain in mediating the membrane localization of KSR1, a crucial feature of its scaffolding activity. Together, these results underscore the functional specificity of these important regulatory domains and demonstrate that the structural features of the C1 domains can provide valuable insight into their ligand-binding properties.
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==About this Structure==
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Solution structure and functional analysis of the cysteine-rich C1 domain of kinase suppressor of Ras (KSR).,Zhou M, Horita DA, Waugh DS, Byrd RA, Morrison DK J Mol Biol. 2002 Jan 18;315(3):435-46. PMID:11786023<ref>PMID:11786023</ref>
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1KBE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1KBE 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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Solution structure and functional analysis of the cysteine-rich C1 domain of kinase suppressor of Ras (KSR)., Zhou M, Horita DA, Waugh DS, Byrd RA, Morrison DK, J Mol Biol. 2002 Jan 18;315(3):435-46. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11786023 11786023]
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</div>
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<div class="pdbe-citations 1kbe" 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>
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Single protein]]
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[[Category: Byrd RA]]
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[[Category: Byrd, R.A.]]
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[[Category: Horita DA]]
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[[Category: Horita, D.A.]]
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[[Category: Morrison DK]]
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[[Category: Morrison, D.K.]]
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[[Category: Waugh DS]]
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[[Category: Waugh, D.S.]]
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[[Category: Zhou M]]
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[[Category: Zhou, M.]]
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[[Category: ZN]]
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[[Category: cysteine-rich domain]]
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[[Category: kinase suppressor of ras]]
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[[Category: ksr]]
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[[Category: zinc-binding protein]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 19:01:26 2007''
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Current revision

Solution structure of the cysteine-rich C1 domain of Kinase Suppressor of Ras

PDB ID 1kbe

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