2r0d

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[[Image:2r0d.jpg|left|200px]]<br /><applet load="2r0d" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2r0d, resolution 2.04&Aring;" />
 
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'''Crystal Structure of Autoinhibited Form of Grp1 Arf GTPase Exchange Factor'''<br />
 
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==Overview==
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==Crystal Structure of Autoinhibited Form of Grp1 Arf GTPase Exchange Factor==
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Arf GTPases regulate membrane trafficking and actin dynamics. Grp1, ARNO, and Cytohesin-1 comprise a family of phosphoinositide-dependent Arf GTPase exchange factors with a Sec7-pleckstrin homology (PH) domain tandem. Here, we report that the exchange activity of the Sec7 domain is potently autoinhibited by conserved elements proximal to the PH domain. The crystal structure of the Grp1 Sec7-PH tandem reveals a pseudosubstrate mechanism of autoinhibition in which the linker region between domains and a C-terminal amphipathic helix physically block the docking sites for the switch regions of Arf GTPases. Mutations within either element result in partial or complete activation. Critical determinants of autoinhibition also contribute to insulin-stimulated plasma membrane recruitment. Autoinhibition can be largely reversed by binding of active Arf6 to Grp1 and by phosphorylation of tandem PKC sites in Cytohesin-1. These observations suggest that Grp1 family GEFs are autoregulated by mechanisms that depend on plasma membrane recruitment for activation.
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<StructureSection load='2r0d' size='340' side='right'caption='[[2r0d]], [[Resolution|resolution]] 2.04&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[2r0d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R0D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R0D FirstGlance]. <br>
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2R0D 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 <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=4IP:'>4IP</scene> and <scene name='pdbligand=PEG:'>PEG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R0D 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]] 2.04&#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=4IP:INOSITOL-(1,3,4,5)-TETRAKISPHOSPHATE'>4IP</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2r0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r0d OCA], [https://pdbe.org/2r0d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r0d RCSB], [https://www.ebi.ac.uk/pdbsum/2r0d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r0d ProSAT]</span></td></tr>
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Structural basis and mechanism of autoregulation in 3-phosphoinositide-dependent Grp1 family Arf GTPase exchange factors., DiNitto JP, Delprato A, Gabe Lee MT, Cronin TC, Huang S, Guilherme A, Czech MP, Lambright DG, Mol Cell. 2007 Nov 30;28(4):569-83. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18042453 18042453]
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CYH3_MOUSE CYH3_MOUSE] Promotes guanine-nucleotide exchange on ARF1. Promotes the activation of ARF factors through replacement of GDP with GTP.<ref>PMID:18042453</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/r0/2r0d_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=2r0d 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>
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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: Cronin TC]]
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[[Category: Cronin, T C.]]
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[[Category: Czech MP]]
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[[Category: Czech, M P.]]
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[[Category: Delprato A]]
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[[Category: Delprato, A.]]
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[[Category: DiNitto JP]]
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[[Category: Dinitto, J P.]]
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[[Category: Gabe Lee MT]]
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[[Category: Guilherme, A.]]
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[[Category: Guilherme A]]
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[[Category: Huang, S.]]
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[[Category: Huang S]]
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[[Category: Lambright, D G.]]
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[[Category: Lambright DG]]
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[[Category: Lee, M T.Gabe.]]
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[[Category: 4IP]]
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[[Category: PEG]]
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[[Category: SO4]]
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[[Category: 3-phosphoinositide]]
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[[Category: arf gtpase]]
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[[Category: coiled coil]]
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[[Category: exchange factor]]
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[[Category: general receptor for phosphoinositides]]
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[[Category: grp1]]
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[[Category: guanine-nucleotide releasing factor]]
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[[Category: pip3]]
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[[Category: signaling protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:43:41 2008''
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Current revision

Crystal Structure of Autoinhibited Form of Grp1 Arf GTPase Exchange Factor

PDB ID 2r0d

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