+Open data
-Basic information
Entry | Database: PDB / ID: 8uqo | |||||||||
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Title | PLCb3-Gbg-Gaq complex on membranes | |||||||||
Components |
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Keywords | SIGNALING PROTEIN / PLCb3 / Gbg / Gaq | |||||||||
Function / homology | Function and homology information phosphoinositide phospholipase C / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / phosphatidylinositol metabolic process / PLC beta mediated events / phospholipase C-activating dopamine receptor signaling pathway / entrainment of circadian clock / regulation of systemic arterial blood pressure / regulation of platelet activation / phosphatidylinositol phospholipase C activity ...phosphoinositide phospholipase C / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / phosphatidylinositol metabolic process / PLC beta mediated events / phospholipase C-activating dopamine receptor signaling pathway / entrainment of circadian clock / regulation of systemic arterial blood pressure / regulation of platelet activation / phosphatidylinositol phospholipase C activity / phototransduction, visible light / phospholipase C activity / glutamate receptor signaling pathway / : / regulation of canonical Wnt signaling pathway / postsynaptic cytosol / Synthesis of IP3 and IP4 in the cytosol / action potential / phosphatidylinositol-mediated signaling / photoreceptor outer segment / lipid catabolic process / release of sequestered calcium ion into cytosol / GTPase activator activity / molecular function activator activity / G protein-coupled receptor binding / negative regulation of protein kinase activity / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / blood coagulation / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / nuclear membrane / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / molecular adaptor activity / calmodulin binding / protein stabilization / cadherin binding / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / calcium ion binding / protein-containing complex binding / GTP binding / Golgi apparatus / signal transduction / protein-containing complex / extracellular exosome / membrane / nucleus / metal ion binding / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.37 Å | |||||||||
Authors | Falzone, M.E. / MacKinnon, R. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2023 Title: The mechanism of regulation of -catalyzed hydrolysis. Authors: Maria E Falzone / Roderick MacKinnon / Abstract: () enzymes cleave phosphatidylinositol 4,5-bisphosphate ( producing and (diacylglycerol). modulates the function of many ion channels, while and regulate intracellular Ca levels and protein ... () enzymes cleave phosphatidylinositol 4,5-bisphosphate ( producing and (diacylglycerol). modulates the function of many ion channels, while and regulate intracellular Ca levels and protein phosphorylation by protein kinase C, respectively. enzymes are under the control of G protein coupled receptor signaling through direct interactions with G proteins and and have been shown to be coincidence detectors for dual stimulation of and -coupled receptors. are aqueous-soluble cytoplasmic enzymes but partition onto the membrane surface to access their lipid substrate, complicating their functional and structural characterization. Using newly developed methods, we recently showed that activates by recruiting it to the membrane. Using these same methods, here we show that increases the catalytic rate constant, , of . Since stimulation of by depends on an autoinhibitory element (the X-Y linker), we propose that produces partial relief of the X-Y linker autoinhibition through an allosteric mechanism. We also determined membrane-bound structures of the and complexes, which show that these G proteins can bind simultaneously and independently of each other to regulate activity. The structures rationalize a finding in the enzyme assay, that costimulation by both G proteins follows a product rule of each independent stimulus. We conclude that baseline activity of is strongly suppressed, but the effect of G proteins, especially acting together, provides a robust stimulus upon G protein stimulation. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8uqo.cif.gz | 379.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8uqo.ent.gz | 289.7 KB | Display | PDB format |
PDBx/mmJSON format | 8uqo.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8uqo_validation.pdf.gz | 1.6 MB | Display | wwPDB validaton report |
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Full document | 8uqo_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 8uqo_validation.xml.gz | 60.3 KB | Display | |
Data in CIF | 8uqo_validation.cif.gz | 90 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uq/8uqo ftp://data.pdbj.org/pub/pdb/validation_reports/uq/8uqo | HTTPS FTP |
-Related structure data
Related structure data | 42476MC 8uqnC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Guanine nucleotide-binding protein ... , 3 types, 5 molecules BCDGA
#1: Protein | Mass: 37416.930 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P62873 #2: Protein | Mass: 8015.310 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: G3V2N0 #3: Protein | | Mass: 41676.387 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAQ / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P50148 |
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-Protein , 1 types, 1 molecules Q
#4: Protein | Mass: 139104.719 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PLCB3 / Production host: Trichoplusia ni (cabbage looper) References: UniProt: Q01970, phosphoinositide phospholipase C |
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-Non-polymers , 5 types, 5 molecules
#5: Chemical | ChemComp-GDP / |
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#6: Chemical | ChemComp-ALF / |
#7: Chemical | ChemComp-MG / |
#8: Chemical | ChemComp-CA / |
#9: Water | ChemComp-HOH / |
-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: PLCb3-Gbg-Gaq complex / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Trichoplusia ni (cabbage looper) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.37 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 359215 / Symmetry type: POINT |