7z3j: Difference between revisions
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==Structure of crystallisable rat Phospholipase C gamma 1 in complex with inositol 1,4,5-trisphosphate== | ==Structure of crystallisable rat Phospholipase C gamma 1 in complex with inositol 1,4,5-trisphosphate== | ||
<StructureSection load='7z3j' size='340' side='right'caption='[[7z3j]]' scene=''> | <StructureSection load='7z3j' size='340' side='right'caption='[[7z3j]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Z3J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z3J FirstGlance]. <br> | <table><tr><td colspan='2'>[[7z3j]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Z3J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z3J FirstGlance]. <br> | ||
</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=7z3j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z3j OCA], [https://pdbe.org/7z3j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z3j RCSB], [https://www.ebi.ac.uk/pdbsum/7z3j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z3j ProSAT]</span></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]] 2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=I3P:D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE'>I3P</scene></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=7z3j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z3j OCA], [https://pdbe.org/7z3j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z3j RCSB], [https://www.ebi.ac.uk/pdbsum/7z3j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z3j ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/PLCG1_RAT PLCG1_RAT] 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 (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
PLCgamma enzymes are autoinhibited in resting cells and form key components of intracellular signaling that are also linked to disease development. Insights into physiological and aberrant activation of PLCgamma require understanding of an active, membrane-bound form, which can hydrolyze inositol-lipid substrates. Here, we demonstrate that PLCgamma1 cannot bind membranes unless the autoinhibition is disrupted. Through extensive molecular dynamics simulations and experimental evidence, we characterize membrane binding by the catalytic core domains and reveal previously unknown sites of lipid interaction. The identified sites act in synergy, overlap with autoinhibitory interfaces, and are shown to be critical for the phospholipase activity in cells. This work provides direct evidence that PLCgamma1 is inhibited through obstruction of its membrane-binding surfaces by the regulatory region and that activation must shift PLCgamma1 to a conformation competent for membrane binding. Knowledge of the critical sites of membrane interaction extends the mechanistic framework for activation, dysregulation, and therapeutic intervention. | |||
Characterization of the membrane interactions of phospholipase Cgamma reveals key features of the active enzyme.,Le Huray KIP, Bunney TD, Pinotsis N, Kalli AC, Katan M Sci Adv. 2022 Jun 24;8(25):eabp9688. doi: 10.1126/sciadv.abp9688. Epub 2022 Jun , 24. PMID:35749497<ref>PMID:35749497</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7z3j" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Phospholipase C|Phospholipase C]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Rattus norvegicus]] | |||
[[Category: Bunney TD]] | [[Category: Bunney TD]] | ||
[[Category: Katan M]] | [[Category: Katan M]] | ||
[[Category: Pinotsis N]] | [[Category: Pinotsis N]] | ||