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Open data
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Basic information
Entry | Database: PDB / ID: 6k41 | |||||||||||||||||||||||||||||||||
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Title | cryo-EM structure of alpha2BAR-GoA complex | |||||||||||||||||||||||||||||||||
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![]() | MEMBRANE PROTEIN / GPCR / Complex / cryo-EM | |||||||||||||||||||||||||||||||||
Function / homology | ![]() Adrenoceptors / Adrenaline signalling through Alpha-2 adrenergic receptor / Surfactant metabolism / Activation of the phototransduction cascade / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / adenylate cyclase-inhibiting adrenergic receptor signaling pathway / Prostacyclin signalling through prostacyclin receptor ...Adrenoceptors / Adrenaline signalling through Alpha-2 adrenergic receptor / Surfactant metabolism / Activation of the phototransduction cascade / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / adenylate cyclase-inhibiting adrenergic receptor signaling pathway / Prostacyclin signalling through prostacyclin receptor / alpha2-adrenergic receptor activity / Adrenaline signalling through Alpha-2 adrenergic receptor / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G alpha (z) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / alpha-2C adrenergic receptor binding / epinephrine binding / positive regulation of uterine smooth muscle contraction / Adrenaline,noradrenaline inhibits insulin secretion / phospholipase C-activating adrenergic receptor signaling pathway / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / G beta:gamma signalling through BTK / Thromboxane signalling through TP receptor / Thrombin signalling through proteinase activated receptors (PARs) / negative regulation of norepinephrine secretion / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / G alpha (s) signalling events / negative regulation of epinephrine secretion / Ca2+ pathway / G alpha (12/13) signalling events / Extra-nuclear estrogen signaling / G alpha (q) signalling events / regulation of vascular associated smooth muscle contraction / Vasopressin regulates renal water homeostasis via Aquaporins / GPER1 signaling / heterotrimeric G-protein binding / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (i) signalling events / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / ADP signalling through P2Y purinoceptor 1 / positive regulation of blood pressure / regulation of smooth muscle contraction / mu-type opioid receptor binding / dopaminergic synapse / corticotropin-releasing hormone receptor 1 binding / 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 / Adrenoceptors / Adrenaline,noradrenaline inhibits insulin secretion / positive regulation of epidermal growth factor receptor signaling pathway / G protein-coupled dopamine receptor signaling pathway / G alpha (z) signalling events / positive regulation of wound healing / spectrin binding / adrenergic receptor signaling pathway / G alpha (i) signalling events / parallel fiber to Purkinje cell synapse / regulation of heart contraction / alkylglycerophosphoethanolamine phosphodiesterase activity / phototransduction, visible light / photoreceptor outer segment / regulation of vasoconstriction / negative regulation of lipid catabolic process / postsynaptic modulation of chemical synaptic transmission / viral release from host cell by cytolysis / cellular response to hormone stimulus / adenylate cyclase-activating adrenergic receptor signaling pathway / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / peptidoglycan catabolic process / cardiac muscle cell apoptotic process / positive regulation of neuron differentiation / presynaptic modulation of chemical synaptic transmission / muscle contraction / positive regulation of cytokine production / locomotory behavior / negative regulation of insulin secretion / female pregnancy / GABA-ergic synapse / platelet activation / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / 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 / G beta:gamma signalling through CDC42 Similarity search - Function | |||||||||||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||||||||||||||||||||||||||
![]() | Yuan, D. / Liu, Z. / Wang, H.W. / Kobilka, B.K. | |||||||||||||||||||||||||||||||||
![]() | ![]() 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
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 211.8 KB | Display | ![]() |
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PDB format | ![]() | 158.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 751.5 KB | Display | ![]() |
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Full document | ![]() | 756.7 KB | Display | |
Data in XML | ![]() | 33.7 KB | Display | |
Data in CIF | ![]() | 52.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9911MC ![]() 9912C ![]() 6k42C C: citing same article ( M: map data used to model this data |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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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.) ![]() ![]() |
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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.) ![]() ![]() ![]() |
#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-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.) ![]() ![]() ![]() ![]() Gene: ADRA2A, e, RB59_126, ADRA2B, ADRA2L1, ADRA2RL1 / Production host: ![]() 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.) ![]() ![]() ![]() |
#6: Chemical | ChemComp-CZX / |
-Details
Has protein modification | 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 |
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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: ![]() |
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 % |
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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: ![]() |
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) |
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Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement |
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EM software | Name: PHENIX / Category: model refinement |
CTF correction | Type: NONE |
3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 258283 / Symmetry type: POINT |