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| - | ==COMPLEX OF RAC2 AND PLCG2 SPPH DOMAIN== | + | |
| - | <StructureSection load='2w2x' size='340' side='right' caption='[[2w2x]], [[Resolution|resolution]] 2.30Å' scene=''> | + | ==Complex of Rac2 and PLCg2 spPH Domain== |
| | + | <StructureSection load='2w2x' size='340' side='right'caption='[[2w2x]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2w2x]] is a 4 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=2W2X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2W2X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2w2x]] 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=2W2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2W2X FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GSP:5-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE'>GSP</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">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2w2v|2w2v]], [[2w2w|2w2w]], [[2w2t|2w2t]], [[1ds6|1ds6]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GSP:5-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE'>GSP</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/Phosphoinositide_phospholipase_C Phosphoinositide phospholipase C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.11 3.1.4.11] </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=2w2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w2x OCA], [https://pdbe.org/2w2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2w2x RCSB], [https://www.ebi.ac.uk/pdbsum/2w2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2w2x 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=2w2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w2x OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2w2x RCSB], [http://www.ebi.ac.uk/pdbsum/2w2x PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/PLCG2_HUMAN PLCG2_HUMAN]] Defects in PLCG2 are the cause of familial cold autoinflammatory syndrome type 3 (FCAS3) [MIM:[http://omim.org/entry/614468 614468]]. An autosomal dominant immune disorder characterized by the development of cutaneous urticaria, erythema, and pruritis in response to cold exposure. Affected individuals have variable additional immunologic defects, including antibody deficiency, decreased numbers of B cells, defective B cells, increased susceptibility to infection, and increased risk of autoimmune disorders.<ref>PMID:22236196</ref> | + | [https://www.uniprot.org/uniprot/RAC2_HUMAN RAC2_HUMAN] Defects in RAC2 are the cause of neutrophil immunodeficiency syndrome (NEUID) [MIM:[https://omim.org/entry/608203 608203].<ref>PMID:10758162</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PLCG2_HUMAN PLCG2_HUMAN]] The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. It is a crucial enzyme in transmembrane signaling. | + | [https://www.uniprot.org/uniprot/RAC2_HUMAN RAC2_HUMAN] Plasma membrane-associated small GTPase which cycles between an active GTP-bound and inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses, such as secretory processes, phagocytose of apoptotic cells and epithelial cell polarization. Augments the production of reactive oxygen species (ROS) by NADPH oxidase.<ref>PMID:1660188</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w2/2w2x_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w2/2w2x_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </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/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </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=2w2x ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2w2x" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Phospholipase C|Phospholipase C]] |
| | + | *[[Rac 3D structures|Rac 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Phosphoinositide phospholipase C]] | + | [[Category: Large Structures]] |
| - | [[Category: Bunney, T D]] | + | [[Category: Bunney TD]] |
| - | [[Category: Opaleye, O]] | + | [[Category: Opaleye O]] |
| - | [[Category: Pearl, L H]] | + | [[Category: Pearl LH]] |
| - | [[Category: Roe, S M]] | + | [[Category: Roe SM]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Phosphoinositide]]
| + | |
| - | [[Category: Phospholipase c]]
| + | |
| - | [[Category: Rac]]
| + | |
| - | [[Category: Rho gtpase]]
| + | |
| - | [[Category: Sh2 domain]]
| + | |
| - | [[Category: Sh3 domain]]
| + | |
| - | [[Category: Signaling protein-hydrolase complex]]
| + | |
| - | [[Category: Signaling protein/hydrolase]]
| + | |
| Structural highlights
Disease
RAC2_HUMAN Defects in RAC2 are the cause of neutrophil immunodeficiency syndrome (NEUID) [MIM:608203.[1]
Function
RAC2_HUMAN Plasma membrane-associated small GTPase which cycles between an active GTP-bound and inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses, such as secretory processes, phagocytose of apoptotic cells and epithelial cell polarization. Augments the production of reactive oxygen species (ROS) by NADPH oxidase.[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
Rho family GTPases are important cellular switches and control a number of physiological functions. Understanding the molecular basis of interaction of these GTPases with their effectors is crucial in understanding their functions in the cell. Here we present the crystal structure of the complex of Rac2 bound to the split pleckstrin homology (spPH) domain of phospholipase C-gamma(2) (PLCgamma(2)). Based on this structure, we illustrate distinct requirements for PLCgamma(2) activation by Rac and EGF and generate Rac effector mutants that specifically block activation of PLCgamma(2), but not the related PLCbeta(2) isoform. Furthermore, in addition to the complex, we report the crystal structures of free spPH and Rac2 bound to GDP and GTPgammaS. These structures illustrate a mechanism of conformational switches that accompany formation of signaling active complexes and highlight the role of effector binding as a common feature of Rac and Cdc42 interactions with a variety of effectors.
Structural insights into formation of an active signaling complex between Rac and phospholipase C gamma 2.,Bunney TD, Opaleye O, Roe SM, Vatter P, Baxendale RW, Walliser C, Everett KL, Josephs MB, Christow C, Rodrigues-Lima F, Gierschik P, Pearl LH, Katan M Mol Cell. 2009 Apr 24;34(2):223-33. PMID:19394299[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ambruso DR, Knall C, Abell AN, Panepinto J, Kurkchubasche A, Thurman G, Gonzalez-Aller C, Hiester A, deBoer M, Harbeck RJ, Oyer R, Johnson GL, Roos D. Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation. Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4654-9. PMID:10758162 doi:10.1073/pnas.080074897
- ↑ Knaus UG, Heyworth PG, Evans T, Curnutte JT, Bokoch GM. Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. Science. 1991 Dec 6;254(5037):1512-5. PMID:1660188
- ↑ Bunney TD, Opaleye O, Roe SM, Vatter P, Baxendale RW, Walliser C, Everett KL, Josephs MB, Christow C, Rodrigues-Lima F, Gierschik P, Pearl LH, Katan M. Structural insights into formation of an active signaling complex between Rac and phospholipase C gamma 2. Mol Cell. 2009 Apr 24;34(2):223-33. PMID:19394299 doi:10.1016/j.molcel.2009.02.023
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