4fbn

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==Insights into structural integration of the PLCgamma regulatory region and mechanism of autoinhibition and activation based on key roles of SH2 domains==
==Insights into structural integration of the PLCgamma regulatory region and mechanism of autoinhibition and activation based on key roles of SH2 domains==
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<StructureSection load='4fbn' size='340' side='right' caption='[[4fbn]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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<StructureSection load='4fbn' size='340' side='right'caption='[[4fbn]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4fbn]] is a 1 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=4FBN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FBN FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4fbn]] is a 1 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=4FBN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FBN FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ey0|4ey0]]</td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PLC1, PLCG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4fbn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fbn OCA], [https://pdbe.org/4fbn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fbn RCSB], [https://www.ebi.ac.uk/pdbsum/4fbn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fbn ProSAT]</span></td></tr>
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<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>
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<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=4fbn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fbn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fbn RCSB], [http://www.ebi.ac.uk/pdbsum/4fbn PDBsum]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/PLCG1_HUMAN PLCG1_HUMAN] Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, FGFR1, FGFR2, FGFR3 and FGFR4. Plays a role in actin reorganization and cell migration.<ref>PMID:17229814</ref>
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Multidomain proteins incorporating interaction domains are central to regulation of cellular processes. The elucidation of structural organization and mechanistic insights into many of these proteins, however, remain challenging due to their inherent flexibility. Here, we describe the organization and function of four interaction domains in PLCgamma1 using a combination of structural biology and biochemical approaches. Intramolecular interactions within the regulatory region center on the cSH2 domain, the only domain that also interacts with the PLC-core. In the context of fibroblast growth-factor receptor signaling, the coordinated involvement of nSH2 and cSH2 domains mediates efficient phosphorylation of PLCgamma1 resulting in the interruption of an autoinhibitory interface by direct competition and, independently, dissociation of PLCgamma1 from the receptor. Further structural insights into the autoinhibitory surfaces provide a framework to interpret gain-of-function mutations in PLCgamma isoforms linked to immune disorders and illustrate a distinct mechanism for regulation of PLC activity by common interaction domains.
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Structural and functional integration of the PLCgamma interaction domains critical for regulatory mechanisms and signaling deregulation.,Bunney TD, Esposito D, Mas-Droux C, Lamber E, Baxendale RW, Martins M, Cole A, Svergun D, Driscoll PC, Katan M Structure. 2012 Dec 5;20(12):2062-75. doi: 10.1016/j.str.2012.09.005. Epub 2012, Oct 11. PMID:23063561<ref>PMID:23063561</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
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</div>
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*[[Phospholipase C|Phospholipase C]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Phosphoinositide phospholipase C]]
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[[Category: Large Structures]]
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[[Category: Bunney, T D]]
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[[Category: Bunney TD]]
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[[Category: Cole, A R]]
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[[Category: Cole AR]]
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[[Category: Katan, M]]
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[[Category: Katan M]]
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[[Category: Mas-Droux, C P]]
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[[Category: Mas-Droux CP]]
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[[Category: Fibroblast growth factor receptor 1]]
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[[Category: Hydrolase]]
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[[Category: Interaction domain]]
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[[Category: Plcgamma specific array]]
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[[Category: Sh2 domain]]
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Insights into structural integration of the PLCgamma regulatory region and mechanism of autoinhibition and activation based on key roles of SH2 domains

PDB ID 4fbn

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