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| | ==Cdc42 complexed with the GTPase binding domain of p21 activated kinase== | | ==Cdc42 complexed with the GTPase binding domain of p21 activated kinase== |
| - | <StructureSection load='1e0a' size='340' side='right'caption='[[1e0a]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1e0a' size='340' side='right'caption='[[1e0a]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1e0a]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E0A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1E0A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1e0a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1E0A FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDC42 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Pak1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Small_monomeric_GTPase Small monomeric GTPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.5.2 3.6.5.2] </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=1e0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e0a OCA], [https://pdbe.org/1e0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1e0a RCSB], [https://www.ebi.ac.uk/pdbsum/1e0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1e0a ProSAT]</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=1e0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e0a OCA], [http://pdbe.org/1e0a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1e0a RCSB], [http://www.ebi.ac.uk/pdbsum/1e0a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1e0a ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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> [[http://www.uniprot.org/uniprot/PAK1_RAT PAK1_RAT]] Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). Plays a role in CTNNB1 signaling. Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2. Phosphorylates MYL9/MLC2 (By similarity).<ref>PMID:9032240</ref> <ref>PMID:9774440</ref> <ref>PMID:9528787</ref> <ref>PMID:12876277</ref> <ref>PMID:14707132</ref> | + | [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 == | | == 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: Buffalo rat]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Small monomeric GTPase]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Laue, E D]] | + | [[Category: Laue ED]] |
| - | [[Category: Lowe, P N]] | + | [[Category: Lowe PN]] |
| - | [[Category: Morreale, A]] | + | [[Category: Morreale A]] |
| - | [[Category: Mott, H R]] | + | [[Category: Mott HR]] |
| - | [[Category: Nietlispach, D]] | + | [[Category: Nietlispach D]] |
| - | [[Category: Owen, D]] | + | [[Category: Owen D]] |
| - | [[Category: Venkatesan, M]] | + | [[Category: Venkatesan M]] |
| - | [[Category: G protein signalling ser/thr kinase]]
| + | |
| - | [[Category: Signalling protein]]
| + | |
| - | [[Category: Signalling protein-kinase complex]]
| + | |
| Structural highlights
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.
Publication Abstract from PubMed
The Rho family GTPases, Cdc42, Rac and Rho, regulate signal transduction pathways via interactions with downstream effector proteins. We report here the solution structure of Cdc42 bound to the GTPase binding domain of alphaPAK, an effector of both Cdc42 and Rac. The structure is compared with those of Cdc42 bound to similar fragments of ACK and WASP, two effector proteins that bind only to Cdc42. The N-termini of all three effector fragments bind in an extended conformation to strand beta2 of Cdc42, and contact helices alpha1 and alpha5. The remaining residues bind to switches I and II of Cdc42, but in a significantly different manner. The structure, together with mutagenesis data, suggests reasons for the specificity of these interactions and provides insight into the mechanism of PAK activation.
Structure of Cdc42 bound to the GTPase binding domain of PAK.,Morreale A, Venkatesan M, Mott HR, Owen D, Nietlispach D, Lowe PN, Laue ED Nat Struct Biol. 2000 May;7(5):384-8. PMID:10802735[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ Morreale A, Venkatesan M, Mott HR, Owen D, Nietlispach D, Lowe PN, Laue ED. Structure of Cdc42 bound to the GTPase binding domain of PAK. Nat Struct Biol. 2000 May;7(5):384-8. PMID:10802735 doi:10.1038/75158
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