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Yorodumi- PDB-6ni3: B2V2R-Gs protein subcomplex of a GPCR-G protein-beta-arrestin meg... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6ni3 | |||||||||
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Title | B2V2R-Gs protein subcomplex of a GPCR-G protein-beta-arrestin mega-complex | |||||||||
Components |
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Keywords | SIGNALING PROTEIN/IMMUNE SYSTEM / GPCR / Gs protein / signaling transducer / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | Function and homology information : / beta2-adrenergic receptor activity / positive regulation of mini excitatory postsynaptic potential / positive regulation of cAMP-dependent protein kinase activity / norepinephrine binding / Adrenoceptors / heat generation / positive regulation of autophagosome maturation / positive regulation of AMPA receptor activity / norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure ...: / beta2-adrenergic receptor activity / positive regulation of mini excitatory postsynaptic potential / positive regulation of cAMP-dependent protein kinase activity / norepinephrine binding / Adrenoceptors / heat generation / positive regulation of autophagosome maturation / positive regulation of AMPA receptor activity / norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure / activation of transmembrane receptor protein tyrosine kinase activity / negative regulation of smooth muscle contraction / positive regulation of lipophagy / response to psychosocial stress / negative regulation of multicellular organism growth / adrenergic receptor signaling pathway / endosome to lysosome transport / diet induced thermogenesis / neuronal dense core vesicle / positive regulation of protein kinase A signaling / PKA activation in glucagon signalling / hair follicle placode formation / adenylate cyclase binding / smooth muscle contraction / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / intracellular transport / D1 dopamine receptor binding / potassium channel regulator activity / Hedgehog 'off' state / positive regulation of bone mineralization / brown fat cell differentiation / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / regulation of sodium ion transport / viral release from host cell by cytolysis / bone resorption / activation of adenylate cyclase activity / adenylate cyclase activator activity / response to cold / peptidoglycan catabolic process / receptor-mediated endocytosis / trans-Golgi network membrane / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / clathrin-coated endocytic vesicle membrane / G-protein beta/gamma-subunit complex binding / bone development / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / positive regulation of protein serine/threonine kinase activity / 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 activation / G protein-coupled acetylcholine receptor signaling pathway / 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 / cognition / 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 / platelet aggregation / 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 / cellular response to amyloid-beta / 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 / extracellular vesicle / sensory perception of smell / cell wall macromolecule catabolic process / signaling receptor complex adaptor activity / Cargo recognition for clathrin-mediated endocytosis / Thrombin signalling through proteinase activated receptors (PARs) / lysozyme / GTPase binding / Clathrin-mediated endocytosis / lysozyme activity Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) Enterobacteria phage RB59 (virus) Lama glama (llama) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
Authors | Nguyen, A.H. / Thomsen, A.R.B. / Cahill, T.J. / des Georges, A. / Lefkowitz, R.J. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Nat Struct Mol Biol / Year: 2019 Title: Structure of an endosomal signaling GPCR-G protein-β-arrestin megacomplex. Authors: Anthony H Nguyen / Alex R B Thomsen / Thomas J Cahill / Rick Huang / Li-Yin Huang / Tara Marcink / Oliver B Clarke / Søren Heissel / Ali Masoudi / Danya Ben-Hail / Fadi Samaan / Venkata P ...Authors: Anthony H Nguyen / Alex R B Thomsen / Thomas J Cahill / Rick Huang / Li-Yin Huang / Tara Marcink / Oliver B Clarke / Søren Heissel / Ali Masoudi / Danya Ben-Hail / Fadi Samaan / Venkata P Dandey / Yong Zi Tan / Chuan Hong / Jacob P Mahoney / Sarah Triest / John Little / Xin Chen / Roger Sunahara / Jan Steyaert / Henrik Molina / Zhiheng Yu / Amedee des Georges / Robert J Lefkowitz / Abstract: Classically, G-protein-coupled receptors (GPCRs) are thought to activate G protein from the plasma membrane and are subsequently desensitized by β-arrestin (β-arr). However, some GPCRs continue to ...Classically, G-protein-coupled receptors (GPCRs) are thought to activate G protein from the plasma membrane and are subsequently desensitized by β-arrestin (β-arr). However, some GPCRs continue to signal through G protein from internalized compartments, mediated by a GPCR-G protein-β-arr 'megaplex'. Nevertheless, the molecular architecture of the megaplex remains unknown. Here, we present its cryo-electron microscopy structure, which shows simultaneous engagement of human G protein and bovine β-arr to the core and phosphorylated tail, respectively, of a single active human chimeric β-adrenergic receptor with the C-terminal tail of the arginine vasopressin type 2 receptor (βVR). All three components adopt their canonical active conformations, suggesting that a single megaplex GPCR is capable of simultaneously activating G protein and β-arr. Our findings provide a structural basis for GPCR-mediated sustained internalized G protein signaling. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6ni3.cif.gz | 266 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6ni3.ent.gz | 200.6 KB | Display | PDB format |
PDBx/mmJSON format | 6ni3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6ni3_validation.pdf.gz | 904.1 KB | Display | wwPDB validaton report |
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Full document | 6ni3_full_validation.pdf.gz | 910.6 KB | Display | |
Data in XML | 6ni3_validation.xml.gz | 33.9 KB | Display | |
Data in CIF | 6ni3_validation.cif.gz | 51.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ni/6ni3 ftp://data.pdbj.org/pub/pdb/validation_reports/ni/6ni3 | HTTPS FTP |
-Related structure data
Related structure data | 9376MC 9375C 9377C 6ni2C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG
#1: Protein | Mass: 44326.160 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAS, GNAS1, GSP / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P63092 |
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#2: Protein | Mass: 38534.062 Da / Num. of mol.: 1 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 |
#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P59768 |
-Protein / Antibody / Non-polymers , 3 types, 3 molecules RN
#4: Protein | Mass: 57630.762 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Enterobacteria phage RB59 (virus), (gene. exp.) Homo sapiens (human) Gene: e, RB59_126, ADRB2, ADRB2R, B2AR / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: A0A097J809, UniProt: P07550, lysozyme |
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#5: Antibody | Mass: 15140.742 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Lama glama (llama) / Production host: Escherichia coli (E. coli) |
#6: Chemical | ChemComp-P0G / |
-Details
Has ligand of interest | Y |
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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 |
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Molecular weight | Units: MEGADALTONS / Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Details: unidentified | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 104 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||
3D reconstruction | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 299893 / Symmetry type: POINT |