+Open data
-Basic information
Entry | Database: PDB / ID: 6k42 | ||||||
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Title | cryo-EM structure of alpha2BAR-Gi1 complex | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / GPCR / Complex / cryo-EM | ||||||
Function / homology | Function and homology information Activation of the phototransduction cascade / Sensory perception of sweet, bitter, and umami (glutamate) taste / regulation of vascular associated smooth muscle contraction / Olfactory Signaling Pathway / negative regulation of uterine smooth muscle contraction / adenylate cyclase-inhibiting adrenergic receptor signaling pathway / phospholipase C-activating adrenergic receptor signaling pathway / alpha2-adrenergic receptor activity / Adrenaline signalling through Alpha-2 adrenergic receptor / G beta:gamma signalling through PLC beta ...Activation of the phototransduction cascade / Sensory perception of sweet, bitter, and umami (glutamate) taste / regulation of vascular associated smooth muscle contraction / Olfactory Signaling Pathway / negative regulation of uterine smooth muscle contraction / adenylate cyclase-inhibiting adrenergic receptor signaling pathway / phospholipase C-activating adrenergic receptor signaling pathway / alpha2-adrenergic receptor activity / Adrenaline signalling through Alpha-2 adrenergic receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / alpha-2C adrenergic receptor binding / receptor transactivation / epinephrine binding / Prostacyclin signalling through prostacyclin receptor / G alpha (z) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G beta:gamma signalling through BTK / Adenylate cyclase inhibitory pathway / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / alpha-1B adrenergic receptor binding / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / positive regulation of uterine smooth muscle contraction / Thromboxane signalling through TP receptor / negative regulation of norepinephrine secretion / Thrombin signalling through proteinase activated receptors (PARs) / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Ca2+ pathway / G alpha (s) signalling events / negative regulation of calcium ion transmembrane transporter activity / negative regulation of epinephrine secretion / G alpha (q) signalling events / Extra-nuclear estrogen signaling / G alpha (12/13) signalling events / heterotrimeric G-protein binding / dopaminergic synapse / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (i) signalling events / GPER1 signaling / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / negative regulation of calcium ion-dependent exocytosis / ADP signalling through P2Y purinoceptor 1 / thermoception / phototransduction, visible light / Surfactant metabolism / positive regulation of potassium ion transport / positive regulation of blood pressure / fear response / positive regulation of membrane protein ectodomain proteolysis / thioesterase binding / negative regulation of insulin secretion involved in cellular response to glucose stimulus / alkylglycerophosphoethanolamine phosphodiesterase activity / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / norepinephrine binding / Adrenoceptors / intestinal absorption / Extra-nuclear estrogen signaling / positive regulation of epidermal growth factor receptor signaling pathway / photoreceptor outer segment membrane / G alpha (i) signalling events / spectrin binding / positive regulation of wound healing / adrenergic receptor signaling pathway / activation of protein kinase activity / Rho protein signal transduction / negative regulation of calcium ion transport / regulation of vasoconstriction / photoreceptor outer segment / GABA-ergic synapse / positive regulation of protein localization to cell cortex / negative regulation of insulin secretion / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / axon terminus / negative regulation of lipid catabolic process / adenylate cyclase-activating adrenergic receptor signaling pathway / presynaptic active zone membrane / regulation of mitotic spindle organization / cellular response to forskolin / cellular response to hormone stimulus / viral release from host cell by cytolysis / cardiac muscle cell apoptotic process / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / positive regulation of neuron differentiation / photoreceptor inner segment / presynaptic modulation of chemical synaptic transmission / activation of protein kinase B activity / peptidoglycan catabolic process / G protein-coupled receptor binding / female pregnancy / G protein-coupled receptor activity / positive regulation of cytokine production Similarity search - Function | ||||||
Biological species | Bos taurus (cattle) Mus musculus (house mouse) Homo sapiens (human) Enterobacteria phage RB59 (virus) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.1 Å | ||||||
Authors | Yuan, D. / Liu, Z. / Wang, H.W. / Kobilka, B.K. | ||||||
Citation | Journal: Nat Chem Biol / Year: 2020 Title: Activation of the α adrenoceptor by the sedative sympatholytic dexmedetomidine. Authors: Daopeng Yuan / Zhongmin Liu / Jonas Kaindl / Shoji Maeda / Jiawei Zhao / Xiaoou Sun / Jun Xu / Peter Gmeiner / Hong-Wei Wang / Brian K Kobilka / Abstract: The α adrenergic receptors (αARs) are G protein-coupled receptors (GPCRs) that respond to adrenaline and noradrenaline and couple to the Gi/o family of G proteins. αARs play important roles in ...The α adrenergic receptors (αARs) are G protein-coupled receptors (GPCRs) that respond to adrenaline and noradrenaline and couple to the Gi/o family of G proteins. αARs play important roles in regulating the sympathetic nervous system. Dexmedetomidine is a highly selective αAR agonist used in post-operative patients as an anxiety-reducing, sedative medicine that decreases the requirement for opioids. As is typical for selective αAR agonists, dexmedetomidine consists of an imidazole ring and a substituted benzene moiety lacking polar groups, which is in contrast to βAR-selective agonists, which share an ethanolamine group and an aromatic system with polar, hydrogen-bonding substituents. To better understand the structural basis for the selectivity and efficacy of adrenergic agonists, we determined the structure of the αAR in complex with dexmedetomidine and Go at a resolution of 2.9 Å by single-particle cryo-EM. The structure reveals the mechanism of αAR-selective activation and provides insights into Gi/o coupling specificity. | ||||||
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 | 6k42.cif.gz | 211.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6k42.ent.gz | 166.2 KB | Display | PDB format |
PDBx/mmJSON format | 6k42.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k4/6k42 ftp://data.pdbj.org/pub/pdb/validation_reports/k4/6k42 | HTTPS FTP |
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-Related structure data
Related structure data | 9912MC 9911C 6k41C C: citing same article (ref.) M: map data used to model this data |
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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: 40415.031 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: GNAI1 / Production host: Spodoptera (butterflies/moths) / References: UniProt: P63097 |
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#2: Protein | Mass: 38530.992 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Gnb1 / Production host: Spodoptera (butterflies/moths) / References: UniProt: P62874 |
#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: Spodoptera (butterflies/moths) / References: UniProt: P59768 |
-Protein / Antibody / Non-polymers , 3 types, 3 molecules RH
#4: Protein | Mass: 58156.211 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human), (gene. exp.) Enterobacteria phage RB59 (virus) Gene: ADRA2A, ADRA2R, ADRAR, e, RB59_126, ADRA2B, ADRA2L1, ADRA2RL1 Production host: Spodoptera (butterflies/moths) References: UniProt: P08913, UniProt: A0A097J809, UniProt: P18089, lysozyme |
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#5: Antibody | Mass: 32898.781 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Spodoptera (butterflies/moths) |
#6: Chemical | ChemComp-CZX / |
-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: 3D ARRAY / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: alpha2BAR-Gi1 complex / Type: COMPLEX / Entity ID: #1-#5 / Source: MULTIPLE SOURCES |
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Molecular weight | Value: 0.15 MDa / Experimental value: YES |
Source (natural) | Organism: Spodoptera (butterflies/moths) |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 10 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % |
-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: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 50 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement |
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CTF correction | Type: NONE |
3D reconstruction | Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 235982 / Symmetry type: POINT |