2wmn

From Proteopedia

(Difference between revisions)

Revision as of 20:24, 25 December 2014

STRUCTURE OF THE COMPLEX BETWEEN DOCK9 AND CDC42-GDP.

Structural highlights

2wmn is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1wg7, 1am4, 1nf3, 1doa, 1aje, 1ki1, 1gzs, 1kzg, 1cee, 2dfk, 1ees, 1an0, 1kz7, 1e0a, 2wm9, 1a4r, 2ase, 1cf4, 2ngr, 1grn, 2wmo
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[DOCK9_HUMAN] Guanine nucleotide-exchange factor (GEF) that activates CDC42 by exchanging bound GDP for free GTP. Overexpression induces filopodia formation.^[1] ^[2] [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.^[3] ^[4] ^[5]

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ 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
↑ 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
↑ 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
↑ 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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2wmn"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2wmn]] is a 2 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WMN FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[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]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[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]]</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2wmn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wmn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wmn RCSB], [http://www.ebi.ac.uk/pdbsum/2wmn PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2wmn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wmn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wmn RCSB], [http://www.ebi.ac.uk/pdbsum/2wmn PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://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>  [[http://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]]
@@ Line 33: / Line 35: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Barford, D.]]
+[[Category: Barford, D]]
-[[Category: Roe, S M.]]
+[[Category: Roe, S M]]
-[[Category: Yang, J.]]
+[[Category: Yang, J]]
 [[Category: Cdc42]]
 [[Category: Cell cycle]]

2wmn

From Proteopedia

Revision as of 20:24, 25 December 2014

STRUCTURE OF THE COMPLEX BETWEEN DOCK9 AND CDC42-GDP.

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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