9y7h: Difference between revisions
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New page: '''Unreleased structure''' The entry 9y7h is ON HOLD Authors: Fisher, I.J., Lyon, A.M. Description: Gb1g2 crosslinked to PLCb3 Category: Unreleased Structures [[Category: Lyon, A.M... |
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The | ==Gb1g2 crosslinked to PLCb3== | ||
<StructureSection load='9y7h' size='340' side='right'caption='[[9y7h]], [[Resolution|resolution]] 4.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9y7h]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9Y7H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9Y7H FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.4Å</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=ME7:1,1-ETHANE-1,2-DIYLBIS(1H-PYRROLE-2,5-DIONE)'>ME7</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=9y7h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9y7h OCA], [https://pdbe.org/9y7h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9y7h RCSB], [https://www.ebi.ac.uk/pdbsum/9y7h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9y7h ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PLCB3_HUMAN PLCB3_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. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Phospholipase C beta (PLCbeta) enzymes are activated by heterotrimeric G protein subunits, increasing hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) at the plasma membrane. All four human PLCbeta isoforms (PLCbeta1-4) are activated by Galpha(q), while PLCbeta1-3 are activated to varying extents by Gbetagamma. The binding sites for Galpha(q) on PLCbeta are well-established and much has been learned about its mechanism of activation, but comparatively little is known about Gbetagamma-dependent activation. In this work, we used cryo-electron microscopy (cryo-EM) single particle analysis (SPA), functional assays, and bioluminescence resonance energy transfer (BRET) to investigate how Gbetagamma interacts with PLCbeta3 in concert with activated Galpha(q) to regulate phospholipase activity. Gbetagamma heterodimers bind multiple surfaces of PLCbeta3 to promote activation but alone do not recruit the enzyme to the plasma membrane. Instead, Gbetagamma facilitates activation by Galpha(q), most likely by reorienting the phospholipase catalytic site at the membrane to maximize PIP2 hydrolysis and downstream Ca(2+) release. Cell-based functional assays demonstrate that Gbetagamma is required for maximal PLCbeta3 activation even when G(q) heterotrimers are the sole source of Gbetagamma. Together, these findings demonstrate that Gbetagamma acts as a critical positive allosteric modulator that regularly acts in concert with Galpha(q) to activate PLCbeta3 at the plasma membrane. | |||
Gbetagamma engages PLCbeta3 at multiple sites to reorient and facilitate its activation.,Fisher IJ, Senarath K, Outlaw K, Muralidharan K, Garland-Kuntz EE, Van Camp M, Komay T, Inoue A, Kostenis E, Lambert NA, Lyon AM bioRxiv [Preprint]. 2026 Jan 14:2026.01.14.699417. doi: , 10.64898/2026.01.14.699417. PMID:41648476<ref>PMID:41648476</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 9y7h" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bos taurus]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Fisher IJ]] | |||
[[Category: Lyon AM]] | |||
