+Open data
-Basic information
Entry | Database: PDB / ID: 6k41 | ||||||
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Title | cryo-EM structure of alpha2BAR-GoA complex | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / GPCR / Complex / cryo-EM | ||||||
Function / homology | Function and homology information regulation of vascular associated smooth muscle contraction / Activation of the phototransduction cascade / Sensory perception of sweet, bitter, and umami (glutamate) taste / Olfactory Signaling Pathway / 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 ...regulation of vascular associated smooth muscle contraction / Activation of the phototransduction cascade / Sensory perception of sweet, bitter, and umami (glutamate) taste / Olfactory Signaling Pathway / 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 / 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) / epinephrine binding / G beta:gamma signalling through BTK / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thromboxane signalling through TP receptor / positive regulation of uterine smooth muscle contraction / negative regulation of norepinephrine secretion / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of epidermal growth factor-activated receptor activity / 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 epinephrine secretion / G alpha (q) signalling events / Extra-nuclear estrogen signaling / G alpha (12/13) signalling events / heterotrimeric G-protein binding / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (i) signalling events / GPER1 signaling / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / regulation of smooth muscle contraction / dopaminergic synapse / ADP signalling through P2Y purinoceptor 1 / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / phototransduction, visible light / positive regulation of blood pressure / fear response / thioesterase binding / negative regulation of insulin secretion involved in cellular response to glucose stimulus / vesicle docking involved in exocytosis / positive regulation of membrane protein ectodomain proteolysis / norepinephrine binding / alkylglycerophosphoethanolamine phosphodiesterase activity / Adrenoceptors / photoreceptor outer segment membrane / regulation of synaptic vesicle exocytosis / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / spectrin binding / positive regulation of wound healing / adrenergic receptor signaling pathway / plasma membrane => GO:0005886 / photoreceptor outer segment / regulation of vasoconstriction / negative regulation of insulin secretion / negative regulation of lipid catabolic process / G protein-coupled serotonin receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / muscle contraction / viral release from host cell by cytolysis / cellular response to hormone stimulus / cardiac muscle cell apoptotic process / positive regulation of neuron differentiation / activation of protein kinase B activity / photoreceptor inner segment / peptidoglycan catabolic process / positive regulation of MAP kinase activity / positive regulation of cytokine production / locomotory behavior / female pregnancy / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / 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 / platelet activation / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Mus musculus (house mouse) Bos taurus (cattle) Enterobacteria phage RB59 (virus) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 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 | 6k41.cif.gz | 205.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6k41.ent.gz | 161.3 KB | Display | PDB format |
PDBx/mmJSON format | 6k41.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6k41_validation.pdf.gz | 717.7 KB | Display | wwPDB validaton report |
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Full document | 6k41_full_validation.pdf.gz | 722.4 KB | Display | |
Data in XML | 6k41_validation.xml.gz | 34.1 KB | Display | |
Data in CIF | 6k41_validation.cif.gz | 52.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k4/6k41 ftp://data.pdbj.org/pub/pdb/validation_reports/k4/6k41 | HTTPS FTP |
-Related structure data
Related structure data | 9911MC 9912C 6k42C 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: 40100.500 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAO1 / Production host: Spodoptera (butterflies/moths) / References: UniProt: P09471 |
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#2: Protein | Mass: 38402.867 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.) Bos taurus (cattle), (gene. exp.) Enterobacteria phage RB59 (virus), (gene. exp.) Homo sapiens (human) Gene: ADRA2A, e, RB59_126, ADRA2B, ADRA2L1, ADRA2RL1 / Production host: Spodoptera (butterflies/moths) References: UniProt: Q28838, 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 / |
-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: alpha2BAR-GoA 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 FIELD |
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: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 258283 / Symmetry type: POINT |