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[[Image:1ki1.gif|left|200px]]<br /><applet load="1ki1" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1ki1, resolution 2.3&Aring;" />
'''Guanine Nucleotide Exchange Region of Intersectin in Complex with Cdc42'''<br />


==Overview==
==Guanine Nucleotide Exchange Region of Intersectin in Complex with Cdc42==
Activation of Rho-family GTPases involves the removal of bound GDP and the, subsequent loading of GTP, all catalyzed by guanine nucleotide exchange, factors (GEFs) of the Dbl-family. Despite high sequence conservation among, Rho GTPases, Dbl proteins possess a wide spectrum of discriminatory, potentials for Rho-family members. To rationalize this specificity, we, have determined crystal structures of the conserved, catalytic fragments, (Dbl and pleckstrin homology domains) of the exchange factors intersectin, and Dbs in complex with their cognate GTPases, Cdc42 and RhoA, respectively. Structure-based mutagenesis of intersectin and Dbs reveals, the key determinants responsible for promoting exchange activity in Cdc42, Rac1 and RhoA. These findings provide critical insight into the structural, features necessary for the proper pairing of Dbl-exchange factors with Rho, GTPases and now allow for the detailed manipulation of signaling pathways, mediated by these oncoproteins in vivo.
<StructureSection load='1ki1' size='340' side='right'caption='[[1ki1]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ki1]] is a 4 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=1KI1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KI1 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=1ki1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ki1 OCA], [https://pdbe.org/1ki1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ki1 RCSB], [https://www.ebi.ac.uk/pdbsum/1ki1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ki1 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CDC42_HUMAN CDC42_HUMAN] Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Plays a role in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. Mediates CDC42-dependent cell migration.<ref>PMID:14978216</ref> <ref>PMID:15642749</ref> <ref>PMID:17038317</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/ki/1ki1_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=1ki1 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1KI1 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 <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KI1 OCA].
*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
 
*[[Intersectin|Intersectin]]
==Reference==
== References ==
Structural basis for the selective activation of Rho GTPases by Dbl exchange factors., Snyder JT, Worthylake DK, Rossman KL, Betts L, Pruitt WM, Siderovski DP, Der CJ, Sondek J, Nat Struct Biol. 2002 Jun;9(6):468-75. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12006984 12006984]
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Der, C.J.]]
[[Category: Der CJ]]
[[Category: Pruitt, W.M.]]
[[Category: Pruitt WM]]
[[Category: Snyder, J.T.]]
[[Category: Snyder JT]]
[[Category: Sondek, J.]]
[[Category: Sondek J]]
[[Category: SO4]]
[[Category: dh domain]]
[[Category: ph domain]]
[[Category: protein-protein complex]]
[[Category: rho gtpase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:13:52 2008''

Latest revision as of 10:25, 14 February 2024

Guanine Nucleotide Exchange Region of Intersectin in Complex with Cdc42Guanine Nucleotide Exchange Region of Intersectin in Complex with Cdc42

Structural highlights

1ki1 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CDC42_HUMAN Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Plays a role in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. Mediates CDC42-dependent cell migration.[1] [2] [3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Gauthier-Campbell C, Bredt DS, Murphy TH, El-Husseini Ael-D. Regulation of dendritic branching and filopodia formation in hippocampal neurons by specific acylated protein motifs. Mol Biol Cell. 2004 May;15(5):2205-17. Epub 2004 Feb 20. PMID:14978216 doi:10.1091/mbc.E03-07-0493
  2. ↑ Oceguera-Yanez F, Kimura K, Yasuda S, Higashida C, Kitamura T, Hiraoka Y, Haraguchi T, Narumiya S. Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis. J Cell Biol. 2005 Jan 17;168(2):221-32. Epub 2005 Jan 10. PMID:15642749 doi:10.1083/jcb.200408085
  3. ↑ Modzelewska K, Newman LP, Desai R, Keely PJ. Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas. J Biol Chem. 2006 Dec 8;281(49):37527-35. Epub 2006 Oct 12. PMID:17038317 doi:10.1074/jbc.M604342200

1ki1, resolution 2.30Å

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