1e0a

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{{STRUCTURE_1e0a| PDB=1e0a | SCENE= }}
 
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===Cdc42 complexed with the GTPase binding domain of p21 activated kinase===
 
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{{ABSTRACT_PUBMED_10802735}}
 
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==Function==
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==Cdc42 complexed with the GTPase binding domain of p21 activated kinase==
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[[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>
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<StructureSection load='1e0a' size='340' side='right'caption='[[1e0a]]' scene=''>
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== Structural highlights ==
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<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>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<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>
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<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>
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</table>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e0/1e0a_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1e0a ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==About this Structure==
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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<ref>PMID:10802735</ref>
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[[1e0a]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://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].
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==See Also==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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*[[GTP-binding protein|GTP-binding protein]]
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</div>
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<div class="pdbe-citations 1e0a" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:010802735</ref><references group="xtra"/><references/>
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*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Laue, E D.]]
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[[Category: Laue ED]]
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[[Category: Lowe, P N.]]
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[[Category: Lowe PN]]
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[[Category: Morreale, A.]]
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[[Category: Morreale A]]
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[[Category: Mott, H R.]]
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[[Category: Mott HR]]
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[[Category: Nietlispach, D.]]
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[[Category: Nietlispach D]]
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[[Category: Owen, D.]]
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[[Category: Owen D]]
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[[Category: Venkatesan, M.]]
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[[Category: Venkatesan M]]
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[[Category: G protein signalling ser/thr kinase]]
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[[Category: Signalling protein]]
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[[Category: Signalling protein-kinase complex]]
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Current revision

Cdc42 complexed with the GTPase binding domain of p21 activated kinase

PDB ID 1e0a

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