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The | ==PLCg2 Split Pleckstrin Homology (PH) Domain== | ||
<StructureSection load='2w2w' size='340' side='right'caption='[[2w2w]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2w2w]] is a 12 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=2W2W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2W2W FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</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=2w2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w2w OCA], [https://pdbe.org/2w2w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2w2w RCSB], [https://www.ebi.ac.uk/pdbsum/2w2w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2w2w ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/PLCG2_HUMAN PLCG2_HUMAN] Defects in PLCG2 are the cause of familial cold autoinflammatory syndrome type 3 (FCAS3) [MIM:[https://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> | |||
== Function == | |||
[https://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. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w2/2w2w_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</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/main_output.php?pdb_ID=2w2w ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:19394299</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2w2w" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Phospholipase C|Phospholipase C]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Bunney TD]] | |||
[[Category: Opaleye O]] | |||
[[Category: Pearl LH]] | |||
[[Category: Roe SM]] | |||
Latest revision as of 18:42, 13 December 2023
PLCg2 Split Pleckstrin Homology (PH) DomainPLCg2 Split Pleckstrin Homology (PH) Domain
Structural highlights
DiseasePLCG2_HUMAN Defects in PLCG2 are the cause of familial cold autoinflammatory syndrome type 3 (FCAS3) [MIM: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.[1] FunctionPLCG2_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. 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 PubMedRho 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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