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1ajw
From Proteopedia
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| - | [[Image:1ajw.jpg|left|200px]]<br /><applet load="1ajw" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="1ajw" /> | ||
| - | '''STRUCTURE OF RHOGDI: A C-TERMINAL BINDING DOMAIN TARGETS AN N-TERMINAL INHIBITORY PEPTIDE TO GTPASES, NMR, 20 STRUCTURES'''<br /> | ||
| - | == | + | ==STRUCTURE OF RHOGDI: A C-TERMINAL BINDING DOMAIN TARGETS AN N-TERMINAL INHIBITORY PEPTIDE TO GTPASES, NMR, 20 STRUCTURES== |
| + | <StructureSection load='1ajw' size='340' side='right'caption='[[1ajw]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1ajw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AJW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AJW FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ajw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ajw OCA], [https://pdbe.org/1ajw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ajw RCSB], [https://www.ebi.ac.uk/pdbsum/1ajw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ajw ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/GDIR1_BOVIN GDIR1_BOVIN] In glioma cells, inhibits cell migration and invasion by mediating the signals of SEMA5A and PLXNB3 that lead to inactivation of RAC1 (By similarity). Regulates the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them.<ref>PMID:2120668</ref> <ref>PMID:9194563</ref> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/aj/1ajw_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </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=1ajw ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
The Rho GDP-dissociation inhibitors (GDIs) negatively regulate Rho-family GTPases. The inhibitory activity of GDI derives both from an ability to bind the carboxy-terminal isoprene of Rho family members and extract them from membranes, and from inhibition of GTPase cycling between the GTP- and GDP-bound states. Here we demonstrate that these binding and inhibitory functions of rhoGDI can be attributed to two structurally distinct regions of the protein. A carboxy-terminal folded domain of relative molecular mass 16,000 (M[r] 16K) binds strongly to the Rho-family member Cdc42, yet has little effect on the rate of nucleotide dissociation from the GTPase. The solution structure of this domain shows a beta-sandwich motif with a narrow hydrophobic cleft that binds isoprenes, and an exposed surface that interacts with the protein portion of Cdc42. The amino-terminal region of rhoGDI is unstructured in the absence of target and contributes little to binding, but is necessary to inhibit nucleotide dissociation from Cdc42. These results lead to a model of rhoGDI function in which the carboxy-terminal binding domain targets the amino-terminal inhibitory region to GTPases, resulting in membrane extraction and inhibition of nucleotide cycling. | The Rho GDP-dissociation inhibitors (GDIs) negatively regulate Rho-family GTPases. The inhibitory activity of GDI derives both from an ability to bind the carboxy-terminal isoprene of Rho family members and extract them from membranes, and from inhibition of GTPase cycling between the GTP- and GDP-bound states. Here we demonstrate that these binding and inhibitory functions of rhoGDI can be attributed to two structurally distinct regions of the protein. A carboxy-terminal folded domain of relative molecular mass 16,000 (M[r] 16K) binds strongly to the Rho-family member Cdc42, yet has little effect on the rate of nucleotide dissociation from the GTPase. The solution structure of this domain shows a beta-sandwich motif with a narrow hydrophobic cleft that binds isoprenes, and an exposed surface that interacts with the protein portion of Cdc42. The amino-terminal region of rhoGDI is unstructured in the absence of target and contributes little to binding, but is necessary to inhibit nucleotide dissociation from Cdc42. These results lead to a model of rhoGDI function in which the carboxy-terminal binding domain targets the amino-terminal inhibitory region to GTPases, resulting in membrane extraction and inhibition of nucleotide cycling. | ||
| - | + | C-terminal binding domain of Rho GDP-dissociation inhibitor directs N-terminal inhibitory peptide to GTPases.,Gosser YQ, Nomanbhoy TK, Aghazadeh B, Manor D, Combs C, Cerione RA, Rosen MK Nature. 1997 Jun 19;387(6635):814-9. PMID:9194563<ref>PMID:9194563</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 1ajw" style="background-color:#fffaf0;"></div> | |
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| - | + | ||
| - | + | ==See Also== | |
| + | *[[Guanine nucleotide dissociation inhibitor|Guanine nucleotide dissociation inhibitor]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Bos taurus]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Gosser YQ]] | ||
| + | [[Category: Rosen MK]] | ||
Current revision
STRUCTURE OF RHOGDI: A C-TERMINAL BINDING DOMAIN TARGETS AN N-TERMINAL INHIBITORY PEPTIDE TO GTPASES, NMR, 20 STRUCTURES
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