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1x86

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(New page: 200px<br /> <applet load="1x86" size="450" color="white" frame="true" align="right" spinBox="true" caption="1x86, resolution 3.22&Aring;" /> '''Crystal Structure o...)
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[[Image:1x86.gif|left|200px]]<br />
 
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<applet load="1x86" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1x86, resolution 3.22&Aring;" />
 
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'''Crystal Structure of the DH/PH domains of Leukemia-associated RhoGEF in complex with RhoA'''<br />
 
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==Overview==
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==Crystal Structure of the DH/PH domains of Leukemia-associated RhoGEF in complex with RhoA==
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Rho guanine-nucleotide exchange factors (RhoGEFs) activate Rho GTPases, and thereby regulate cytoskeletal structure, gene transcription, and cell, migration. Leukemia-associated RhoGEF (LARG) belongs to a small subfamily, of RhoGEFs that are RhoA-selective and directly activated by the, Galpha12/13 family of heterotrimeric G proteins. Herein we describe the, atomic structures of the catalytic Dbl homology (DH) and pleckstrin, homology (PH) domains of LARG alone and in complex with RhoA. These, structures demonstrate that the DH/PH domains of LARG can undergo a, dramatic conformational change upon binding RhoA, wherein both the DH and, PH domains directly engage RhoA. Through mutational analysis we show that, full nucleotide exchange activity requires a novel N-terminal extension on, the DH domain that is predicted to exist in a broader family of RhoGEFs, that includes p115-RhoGEF, Lbc, Lfc, Net1, and Xpln, and identify regions, within the LARG PH domain that contribute to its ability to facilitate, nucleotide exchange in vitro. In crystals of the DH/PH-RhoA complex, the, active site of RhoA adopts two distinct GDP-excluding conformations among, the four unique complexes in the asymmetric unit. Similar changes were, previously observed in structures of nucleotide-free Ras and Ef-Tu. A, potential protein-docking site on the LARG PH domain is also evident and, appears to be conserved throughout the Lbc subfamily of RhoGEFs.
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<StructureSection load='1x86' size='340' side='right'caption='[[1x86]], [[Resolution|resolution]] 3.22&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1x86]] is a 8 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=1X86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1X86 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]] 3.22&#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=PO4:PHOSPHATE+ION'>PO4</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=1x86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x86 OCA], [https://pdbe.org/1x86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1x86 RCSB], [https://www.ebi.ac.uk/pdbsum/1x86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1x86 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/ARHGC_HUMAN ARHGC_HUMAN] Note=A chromosomal aberration involving ARHGEF12 may be a cause of acute leukemia. Translocation t(11;11)(q23;23) with MLL.
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== Function ==
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[https://www.uniprot.org/uniprot/ARHGC_HUMAN ARHGC_HUMAN] May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13.<ref>PMID:11094164</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/x8/1x86_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=1x86 ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known diseases associated with this structure: Leukemia, acute myeloid OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604763 604763]]
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*[[Rho GTPase 3D structures|Rho GTPase 3D structures]]
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*[[Rho guanine nucleotide exchange factor 3D structures|Rho guanine nucleotide exchange factor 3D structures]]
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==About this Structure==
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== References ==
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1X86 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 PO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1X86 OCA].
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<references/>
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__TOC__
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==Reference==
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</StructureSection>
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Structural determinants of RhoA binding and nucleotide exchange in leukemia-associated Rho guanine-nucleotide exchange factor., Kristelly R, Gao G, Tesmer JJ, J Biol Chem. 2004 Nov 5;279(45):47352-62. Epub 2004 Aug 25. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15331592 15331592]
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[[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: Gao, G.]]
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[[Category: Gao G]]
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[[Category: Kristelly, R.]]
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[[Category: Kristelly R]]
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[[Category: Tesmer, J.J.]]
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[[Category: Tesmer JJ]]
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[[Category: PO4]]
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[[Category: alpha/beta (rhoa)]]
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[[Category: beta sandwich (ph)]]
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[[Category: helical bundle (dh)]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:02:12 2007''
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Current revision

Crystal Structure of the DH/PH domains of Leukemia-associated RhoGEF in complex with RhoA

PDB ID 1x86

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