Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Molecular basis for Gβγ-mediated activation of phosphoinositide 3-kinase γ.
Journal, issue, pages	Nat Struct Mol Biol, Vol. 31, Issue 8, Page 1198-1207, Year 2024
Publish date	Apr 2, 2024
Authors	Chun-Liang Chen / Ramizah Syahirah / Sandeep K Ravala / Yu-Chen Yen / Thomas Klose / Qing Deng / John J G Tesmer /
PubMed Abstract	The conversion of phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-triphosphate by phosphoinositide 3-kinase γ (PI3Kγ) is critical for neutrophil chemotaxis and cancer metastasis. ...The conversion of phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-triphosphate by phosphoinositide 3-kinase γ (PI3Kγ) is critical for neutrophil chemotaxis and cancer metastasis. PI3Kγ is activated by Gβγ heterodimers released from G protein-coupled receptors responding to extracellular signals. Here we determined cryo-electron microscopy structures of Sus scrofa PI3Kγ-human Gβγ complexes in the presence of substrates/analogs, revealing two Gβγ binding sites: one on the p110γ helical domain and another on the p101 C-terminal domain. Comparison with PI3Kγ alone reveals conformational changes in the kinase domain upon Gβγ binding that are similar to Ras·GTP-induced changes. Assays of variants perturbing the Gβγ binding sites and interdomain contacts altered by Gβγ binding suggest that Gβγ 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 Gβγ-mediated activation mechanisms in this enzyme family and drug development for PI3Kγ.
External links	Nat Struct Mol Biol / PubMed:38565696 / PubMed Central
Methods	EM (single particle)
Resolution	3.03 - 3.9 Å
Structure data	40650 8so9 EMDB-40650, PDB-8so9: Phosphoinositide phosphate 3 kinase gamma Method: EM (single particle) / Resolution: 3.03 Å 40651 8soa EMDB-40651, PDB-8soa: Phosphoinositide phosphate 3 kinase gamma bound with ATP Method: EM (single particle) / Resolution: 3.32 Å 40652 8sob EMDB-40652, PDB-8sob: Phosphoinositide phosphate 3 kinase gamma bound with ADP Method: EM (single particle) / Resolution: 3.9 Å 40653 8soc EMDB-40653, PDB-8soc: Phosphoinositide phosphate 3 kinase gamma bound with ADP and Gbetagamma Method: EM (single particle) / Resolution: 3.5 Å 40654 8sod EMDB-40654, PDB-8sod: Phosphoinositide phosphate 3 kinase gamma bound with ADP and two Gbetagamma subunits in State 1 Method: EM (single particle) / Resolution: 3.4 Å 40655 8soe EMDB-40655, PDB-8soe: Phosphoinositide phosphate 3 kinase gamma bound with ADP and two Gbetagamma subunits in State 2 Method: EM (single particle) / Resolution: 3.6 Å
Chemicals	ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying moleculeYM ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying moleculeYM
Source	sus scrofa (pig) bos taurus (cattle)
Keywords	SIGNALING PROTEIN / Phosphoinositide 3-Kinase / Chemotaxis / Cancer