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New page: left|200px<br /><applet load="1ajw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ajw" /> '''STRUCTURE OF RHOGDI: A C-TERMINAL BINDING DO...
 
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[[Image:1ajw.jpg|left|200px]]<br /><applet load="1ajw" size="450" color="white" frame="true" align="right" spinBox="true"
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'''STRUCTURE OF RHOGDI: A C-TERMINAL BINDING DOMAIN TARGETS AN N-TERMINAL INHIBITORY PEPTIDE TO GTPASES, NMR, 20 STRUCTURES'''<br />


==Overview==
==STRUCTURE OF RHOGDI: A C-TERMINAL BINDING DOMAIN TARGETS AN N-TERMINAL INHIBITORY PEPTIDE TO GTPASES, NMR, 20 STRUCTURES==
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.
<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.


==About this Structure==
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>
1AJW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1AJW OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9194563 9194563]
</div>
<div class="pdbe-citations 1ajw" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Guanine nucleotide dissociation inhibitor|Guanine nucleotide dissociation inhibitor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Gosser, Y.Q.]]
[[Category: Gosser YQ]]
[[Category: Rosen, M.K.]]
[[Category: Rosen MK]]
[[Category: isoprene binding]]
[[Category: nucleotide exchange]]
[[Category: rho-gtpase inhibitor]]
 
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