2r09

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[[Image:2r09.jpg|left|200px]]
 
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==Crystal Structure of Autoinhibited Form of Grp1 Arf GTPase Exchange Factor==
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The line below this paragraph, containing "STRUCTURE_2r09", creates the "Structure Box" on the page.
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<StructureSection load='2r09' size='340' side='right'caption='[[2r09]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2r09]] 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=2R09 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R09 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]] 1.9&#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=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=PE5:3,6,9,12,15,18,21,24-OCTAOXAHEXACOSAN-1-OL'>PE5</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_2r09| PDB=2r09 | SCENE= }}
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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=2r09 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r09 OCA], [https://pdbe.org/2r09 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r09 RCSB], [https://www.ebi.ac.uk/pdbsum/2r09 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r09 ProSAT]</span></td></tr>
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</table>
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'''Crystal Structure of Autoinhibited Form of Grp1 Arf GTPase Exchange Factor'''
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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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==Overview==
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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/r0/2r09_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=2r09 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 ==
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.
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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==About this Structure==
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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:18042453<ref>PMID:18042453</ref>
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2R09 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R09 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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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://www.ncbi.nlm.nih.gov/pubmed/18042453 18042453]
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</div>
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<div class="pdbe-citations 2r09" 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: 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: 3-phosphoinositide]]
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[[Category: Arf]]
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[[Category: Autoinhibition]]
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[[Category: Coiled coil]]
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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: Pleckstrin homology domain]]
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[[Category: Signaling protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 16:00:50 2008''
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Current revision

Crystal Structure of Autoinhibited Form of Grp1 Arf GTPase Exchange Factor

PDB ID 2r09

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