1zc3

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[[Image:1zc3.gif|left|200px]]<br /><applet load="1zc3" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1zc3, resolution 2.00&Aring;" />
 
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'''Crystal structure of the Ral-binding domain of Exo84 in complex with the active RalA'''<br />
 
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==Overview==
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==Crystal structure of the Ral-binding domain of Exo84 in complex with the active RalA==
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The Sec6/8 complex, also known as the exocyst complex, is an octameric protein complex that has been implicated in tethering of secretory vesicles to specific regions on the plasma membrane. Two subunits of the Sec6/8 complex, Exo84 and Sec5, have recently been shown to be effector targets for active Ral GTPases. However, the mechanism by which Ral proteins regulate the Sec6/8 activities remains unclear. Here, we present the crystal structure of the Ral-binding domain of Exo84 in complex with active RalA. The structure reveals that the Exo84 Ral-binding domain adopts a pleckstrin homology domain fold, and that RalA interacts with Exo84 via an extended interface that includes both switch regions. Key residues of Exo84 and RalA were found that determine the specificity of the complex interactions; these interactions were confirmed by mutagenesis binding studies. Structural and biochemical data show that Exo84 and Sec5 competitively bind to active RalA. Taken together, these results further strengthen the proposed role of RalA-regulated assembly of the Sec6/8 complex.
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<StructureSection load='1zc3' size='340' side='right'caption='[[1zc3]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[1zc3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZC3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZC3 FirstGlance]. <br>
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1ZC3 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/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=GNP:'>GNP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZC3 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&#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=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=1zc3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zc3 OCA], [https://pdbe.org/1zc3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zc3 RCSB], [https://www.ebi.ac.uk/pdbsum/1zc3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zc3 ProSAT]</span></td></tr>
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Exo84 and Sec5 are competitive regulatory Sec6/8 effectors to the RalA GTPase., Jin R, Junutula JR, Matern HT, Ervin KE, Scheller RH, Brunger AT, EMBO J. 2005 Jun 15;24(12):2064-74. Epub 2005 May 26. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15920473 15920473]
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/RALA_HUMAN RALA_HUMAN] Multifunctional GTPase involved in a variety of cellular processes including gene expression, cell migration, cell proliferation, oncogenic transformation and membrane trafficking. Accomplishes its multiple functions by interacting with distinct downstream effectors. Acts as a GTP sensor for GTP-dependent exocytosis of dense core vesicles. Plays a role in the early stages of cytokinesis and is required to tether the exocyst to the cytokinetic furrow. The RALA-exocyst complex regulates integrin-dependent membrane raft exocytosis and growth signaling. Key regulator of LPAR1 signaling and competes with ADRBK1 for binding to LPAR1 thus affecting the signaling properties of the receptor. Required for anchorage-independent proliferation of transformed cells.<ref>PMID:18756269</ref> <ref>PMID:19306925</ref> <ref>PMID:20005108</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/zc/1zc3_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=1zc3 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]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Brunger, A T.]]
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[[Category: Brunger AT]]
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[[Category: Ervin, K E.]]
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[[Category: Ervin KE]]
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[[Category: Jin, R.]]
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[[Category: Jin R]]
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[[Category: Junutula, J R.]]
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[[Category: Junutula JR]]
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[[Category: Matern, H T.]]
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[[Category: Matern HT]]
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[[Category: Scheller, R H.]]
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[[Category: Scheller RH]]
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[[Category: GNP]]
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[[Category: MG]]
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[[Category: exocytosis]]
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[[Category: gtp-binding protein]]
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[[Category: small gtpase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:14:06 2008''
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Current revision

Crystal structure of the Ral-binding domain of Exo84 in complex with the active RalA

PDB ID 1zc3

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