View source for 8soe


==Phosphoinositide phosphate 3 kinase gamma bound with ADP and two Gbetagamma subunits in State 2==
<StructureSection load='8soe' size='340' side='right'caption='[[8soe]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8soe]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SOE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SOE 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]] 3.6&#8491;</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=8soe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8soe OCA], [https://pdbe.org/8soe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8soe RCSB], [https://www.ebi.ac.uk/pdbsum/8soe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8soe ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PI3R5_PIG PI3R5_PIG] Regulatory subunit of the PI3K gamma complex. Required for recruitment of the catalytic subunit to the plasma membrane via interaction with beta-gamma G protein dimers. Required for G protein-mediated activation of PIK3CG.<ref>PMID:12507995</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The conversion of phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-triphosphate by phosphoinositide 3-kinase gamma (PI3Kgamma) is critical for neutrophil chemotaxis and cancer metastasis. PI3Kgamma is activated by Gbetagamma heterodimers released from G protein-coupled receptors responding to extracellular signals. Here we determined cryo-electron microscopy structures of Sus scrofa PI3Kgamma-human Gbetagamma complexes in the presence of substrates/analogs, revealing two Gbetagamma binding sites: one on the p110gamma helical domain and another on the p101 C-terminal domain. Comparison with PI3Kgamma alone reveals conformational changes in the kinase domain upon Gbetagamma binding that are similar to Ras.GTP-induced changes. Assays of variants perturbing the Gbetagamma binding sites and interdomain contacts altered by Gbetagamma binding suggest that Gbetagamma recruits the enzyme to membranes and allosterically regulates activity via both sites. Studies of zebrafish neutrophil migration align with these findings, paving the way for in-depth investigation of Gbetagamma-mediated activation mechanisms in this enzyme family and drug development for PI3Kgamma.

Molecular basis for Gbetagamma-mediated activation of phosphoinositide 3-kinase gamma.,Chen CL, Syahirah R, Ravala SK, Yen YC, Klose T, Deng Q, Tesmer JJG Nat Struct Mol Biol. 2024 Aug;31(8):1198-1207. doi: 10.1038/s41594-024-01265-y. , Epub 2024 Apr 2. PMID:38565696<ref>PMID:38565696</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8soe" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Chen C-L]]
[[Category: Tesmer JJG]]