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| | <StructureSection load='2wmn' size='340' side='right'caption='[[2wmn]], [[Resolution|resolution]] 2.39Å' scene=''> | | <StructureSection load='2wmn' size='340' side='right'caption='[[2wmn]], [[Resolution|resolution]] 2.39Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2wmn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WMN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WMN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2wmn]] is a 2 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=2WMN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WMN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.391Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1wg7|1wg7]], [[1am4|1am4]], [[1nf3|1nf3]], [[1doa|1doa]], [[1aje|1aje]], [[1ki1|1ki1]], [[1gzs|1gzs]], [[1kzg|1kzg]], [[1cee|1cee]], [[2dfk|2dfk]], [[1ees|1ees]], [[1an0|1an0]], [[1kz7|1kz7]], [[1e0a|1e0a]], [[2wm9|2wm9]], [[1a4r|1a4r]], [[2ase|2ase]], [[1cf4|1cf4]], [[2ngr|2ngr]], [[1grn|1grn]], [[2wmo|2wmo]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</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=2wmn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wmn OCA], [https://pdbe.org/2wmn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wmn RCSB], [https://www.ebi.ac.uk/pdbsum/2wmn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wmn ProSAT]</span></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=2wmn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wmn OCA], [https://pdbe.org/2wmn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wmn RCSB], [https://www.ebi.ac.uk/pdbsum/2wmn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wmn ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DOCK9_HUMAN DOCK9_HUMAN]] Guanine nucleotide-exchange factor (GEF) that activates CDC42 by exchanging bound GDP for free GTP. Overexpression induces filopodia formation.<ref>PMID:12172552</ref> <ref>PMID:19745154</ref>
| + | [https://www.uniprot.org/uniprot/DOCK9_HUMAN DOCK9_HUMAN] Guanine nucleotide-exchange factor (GEF) that activates CDC42 by exchanging bound GDP for free GTP. Overexpression induces filopodia formation.<ref>PMID:12172552</ref> <ref>PMID:19745154</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Barford, D]] | + | [[Category: Barford D]] |
| - | [[Category: Roe, S M]] | + | [[Category: Roe SM]] |
| - | [[Category: Yang, J]] | + | [[Category: Yang J]] |
| - | [[Category: Alternative splicing]]
| + | |
| - | [[Category: Cdc42]]
| + | |
| - | [[Category: Cell cycle]]
| + | |
| - | [[Category: Cell membrane]]
| + | |
| - | [[Category: Coiled coil]]
| + | |
| - | [[Category: Dock9]]
| + | |
| - | [[Category: Gef]]
| + | |
| - | [[Category: Gtp-binding]]
| + | |
| - | [[Category: Guanine-nucleotide releasing factor]]
| + | |
| - | [[Category: Lipoprotein]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Methylation]]
| + | |
| - | [[Category: Nucleotide]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Polymorphism]]
| + | |
| - | [[Category: Prenylation]]
| + | |
| Structural highlights
Function
DOCK9_HUMAN Guanine nucleotide-exchange factor (GEF) that activates CDC42 by exchanging bound GDP for free GTP. Overexpression induces filopodia formation.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Activation of Rho guanosine triphosphatases (GTPases) to the guanine triphosphate (GTP)-bound state is a critical event in their regulation of the cytoskeleton and cell signaling. Members of the DOCK family of guanine nucleotide exchange factors (GEFs) are important activators of Rho GTPases, but the mechanism of activation by their catalytic DHR2 domain is unknown. Through structural analysis of DOCK9-Cdc42 complexes, we identify a nucleotide sensor within the alpha10 helix of the DHR2 domain that contributes to release of guanine diphosphate (GDP) and then to discharge of the activated GTP-bound Cdc42. Magnesium exclusion, a critical factor in promoting GDP release, is mediated by a conserved valine residue within this sensor, whereas binding of GTP-Mg2+ to the nucleotide-free complex results in magnesium-inducing displacement of the sensor to stimulate discharge of Cdc42-GTP. These studies identify an unusual mechanism of GDP release and define the complete GEF catalytic cycle from GDP dissociation followed by GTP binding and discharge of the activated GTPase.
Activation of Rho GTPases by DOCK exchange factors is mediated by a nucleotide sensor.,Yang J, Zhang Z, Roe SM, Marshall CJ, Barford D Science. 2009 Sep 11;325(5946):1398-402. PMID:19745154[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Meller N, Irani-Tehrani M, Kiosses WB, Del Pozo MA, Schwartz MA. Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins. Nat Cell Biol. 2002 Sep;4(9):639-47. PMID:12172552 doi:http://dx.doi.org/10.1038/ncb835
- ↑ Yang J, Zhang Z, Roe SM, Marshall CJ, Barford D. Activation of Rho GTPases by DOCK exchange factors is mediated by a nucleotide sensor. Science. 2009 Sep 11;325(5946):1398-402. PMID:19745154 doi:325/5946/1398
- ↑ Yang J, Zhang Z, Roe SM, Marshall CJ, Barford D. Activation of Rho GTPases by DOCK exchange factors is mediated by a nucleotide sensor. Science. 2009 Sep 11;325(5946):1398-402. PMID:19745154 doi:325/5946/1398
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