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New page: left|200px<br /><applet load="2bye" size="450" color="white" frame="true" align="right" spinBox="true" caption="2bye" /> '''NMR SOLUTION STRUCTURE OF PHOSPHOLIPASE C EP...
 
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[[Image:2bye.gif|left|200px]]<br /><applet load="2bye" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2bye" />
'''NMR SOLUTION STRUCTURE OF PHOSPHOLIPASE C EPSILON RA 1 DOMAIN'''<br />


==Overview==
==NMR solution structure of phospholipase c epsilon RA 1 domain==
Ras proteins signal to a number of distinct pathways by interacting with, diverse effectors. Studies of ras/effector interactions have focused on, three classes, Raf kinases, ral guanylnucleotide-exchange factors, and, phosphatidylinositol-3-kinases. Here we describe ras interactions with, another effector, the recently identified phospholipase C epsilon, (PLCepsilon). We solved structures of PLCepsilon RA domains (RA1 and RA2), by NMR and the structure of the RA2/ras complex by X-ray crystallography., Although the similarity between ubiquitin-like folds of RA1 and RA2 proves, that they are homologs, only RA2 can bind ras. Some of the features of the, RA2/ras interface are unique to PLCepsilon, while the ability to make, contacts with both switch I and II regions of ras is shared only with, phosphatidylinositol-3-kinase. Studies of PLCepsilon regulation suggest, that, in a cellular context, the RA2 domain, in a mode specific to, PLCepsilon, has a role in membrane targeting with further regulatory, impact on PLC activity.
<StructureSection load='2bye' size='340' side='right'caption='[[2bye]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2bye]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BYE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BYE FirstGlance]. <br>
</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2bye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bye OCA], [https://pdbe.org/2bye PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bye RCSB], [https://www.ebi.ac.uk/pdbsum/2bye PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bye ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PLCE1_HUMAN PLCE1_HUMAN] Familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial sclerosis;Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/PLCE1_HUMAN PLCE1_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. PLCE1 is a bifunctional enzyme which also regulates small GTPases of the Ras superfamily through its Ras guanine-exchange factor (RasGEF) activity. As an effector of heterotrimeric and small G-protein, it may play a role in cell survival, cell growth, actin organization and T-cell activation.<ref>PMID:11022047</ref> <ref>PMID:11395506</ref> <ref>PMID:11715024</ref> <ref>PMID:11877431</ref> <ref>PMID:12721365</ref> <ref>PMID:16537651</ref> <ref>PMID:17086182</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ras proteins signal to a number of distinct pathways by interacting with diverse effectors. Studies of ras/effector interactions have focused on three classes, Raf kinases, ral guanylnucleotide-exchange factors, and phosphatidylinositol-3-kinases. Here we describe ras interactions with another effector, the recently identified phospholipase C epsilon (PLCepsilon). We solved structures of PLCepsilon RA domains (RA1 and RA2) by NMR and the structure of the RA2/ras complex by X-ray crystallography. Although the similarity between ubiquitin-like folds of RA1 and RA2 proves that they are homologs, only RA2 can bind ras. Some of the features of the RA2/ras interface are unique to PLCepsilon, while the ability to make contacts with both switch I and II regions of ras is shared only with phosphatidylinositol-3-kinase. Studies of PLCepsilon regulation suggest that, in a cellular context, the RA2 domain, in a mode specific to PLCepsilon, has a role in membrane targeting with further regulatory impact on PLC activity.


==About this Structure==
Structural and mechanistic insights into ras association domains of phospholipase C epsilon.,Bunney TD, Harris R, Gandarillas NL, Josephs MB, Roe SM, Sorli SC, Paterson HF, Rodrigues-Lima F, Esposito D, Ponting CP, Gierschik P, Pearl LH, Driscoll PC, Katan M Mol Cell. 2006 Feb 17;21(4):495-507. PMID:16483931<ref>PMID:16483931</ref>
2BYE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BYE OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Structural and mechanistic insights into ras association domains of phospholipase C epsilon., Bunney TD, Harris R, Gandarillas NL, Josephs MB, Roe SM, Sorli SC, Paterson HF, Rodrigues-Lima F, Esposito D, Ponting CP, Gierschik P, Pearl LH, Driscoll PC, Katan M, Mol Cell. 2006 Feb 17;21(4):495-507. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16483931 16483931]
</div>
<div class="pdbe-citations 2bye" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Phospholipase C|Phospholipase C]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Bunney, T.D.]]
[[Category: Bunney TD]]
[[Category: Driscoll, P.C.]]
[[Category: Driscoll PC]]
[[Category: Esposito, D.]]
[[Category: Esposito D]]
[[Category: Gandarillas, N.L.]]
[[Category: Gandarillas NL]]
[[Category: Gieschik, P.]]
[[Category: Gieschik P]]
[[Category: Harris, R.]]
[[Category: Harris R]]
[[Category: Josephs, M.B.]]
[[Category: Josephs MB]]
[[Category: Katan, M.]]
[[Category: Katan M]]
[[Category: Paterson, H.F.]]
[[Category: Paterson HF]]
[[Category: Pearl, L.H.]]
[[Category: Pearl LH]]
[[Category: Rodrigues-Lima, F.]]
[[Category: Rodrigues-Lima F]]
[[Category: Roe, S.M.]]
[[Category: Roe SM]]
[[Category: lipase]]
[[Category: phospholipase c epsilon]]
[[Category: ras association domain]]
[[Category: ubiquitin superfold]]
 
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