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Yorodumi- PDB-7ejk: Structure of the alpha2A-adrenergic receptor GoA signaling comple... -
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-Basic information
Entry | Database: PDB / ID: 7ejk | ||||||
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Title | Structure of the alpha2A-adrenergic receptor GoA signaling complex bound to oxymetazoline | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / alpha2A-adrenergic receptor / signaling complex / cryo-EM | ||||||
Function / homology | Function and homology information 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 / alpha-2C adrenergic receptor binding / receptor transactivation / epinephrine binding / alpha-1B adrenergic receptor binding / negative regulation of norepinephrine secretion ...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 / alpha-2C adrenergic receptor binding / receptor transactivation / epinephrine binding / alpha-1B adrenergic receptor binding / negative regulation of norepinephrine secretion / negative regulation of calcium ion transmembrane transporter activity / negative regulation of epinephrine secretion / heterotrimeric G-protein binding / negative regulation of calcium ion-dependent exocytosis / dopaminergic synapse / mu-type opioid receptor binding / Surfactant metabolism / positive regulation of potassium ion transport / corticotropin-releasing hormone receptor 1 binding / thermoception / fear response / thioesterase binding / negative regulation of insulin secretion involved in cellular response to glucose stimulus / vesicle docking involved in exocytosis / intestinal absorption / positive regulation of membrane protein ectodomain proteolysis / norepinephrine binding / Adrenoceptors / positive regulation of epidermal growth factor receptor signaling pathway / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / positive regulation of wound healing / activation of protein kinase activity / adrenergic receptor signaling pathway / adenylate cyclase-activating adrenergic receptor signaling pathway / negative regulation of calcium ion transport / Rho protein signal transduction / regulation of vasoconstriction / negative regulation of insulin secretion / negative regulation of lipid catabolic process / G protein-coupled serotonin receptor binding / GABA-ergic synapse / muscle contraction / cellular response to hormone stimulus / presynaptic active zone membrane / axon terminus / presynaptic modulation of chemical synaptic transmission / activation of protein kinase B activity / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / positive regulation of cytokine production / female pregnancy / locomotory behavior / adenylate cyclase-activating G protein-coupled receptor signaling pathway / postsynaptic density membrane / positive regulation of MAP kinase activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / platelet activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G beta:gamma signalling through CDC42 / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / vasodilation / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / glucose homeostasis / retina development in camera-type eye Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | ||||||
Authors | Xu, J. / Cao, S. / Liu, Z. / Du, Y. | ||||||
Citation | Journal: Sci Adv / Year: 2022 Title: Structural insights into ligand recognition, activation, and signaling of the α adrenergic receptor. Authors: Jun Xu / Sheng Cao / Harald Hübner / Dorothée Weikert / Geng Chen / Qiuyuan Lu / Daopeng Yuan / Peter Gmeiner / Zheng Liu / Yang Du / Abstract: The α adrenergic receptor (αAR) is a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor that mediates important physiological functions in response to the endogenous ...The α adrenergic receptor (αAR) is a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor that mediates important physiological functions in response to the endogenous neurotransmitters norepinephrine and epinephrine, as well as numerous chemically distinct drugs. However, the molecular mechanisms of drug actions remain poorly understood. Here, we report the cryo-electron microscopy structures of the human αAR-GoA complex bound to norepinephrine and three imidazoline derivatives (brimonidine, dexmedetomidine, and oxymetazoline). Together with mutagenesis and functional data, these structures provide important insights into the molecular basis of ligand recognition, activation, and signaling at the αAR. Further structural analyses uncover different molecular determinants between αAR and βARs for recognition of norepinephrine and key regions that determine the G protein coupling selectivity. Overall, our studies provide a framework for understanding the signal transduction of the adrenergic system at the atomic level, which will facilitate rational structure-based discovery of safer and more effective medications for αAR. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7ejk.cif.gz | 206.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7ejk.ent.gz | 161.5 KB | Display | PDB format |
PDBx/mmJSON format | 7ejk.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7ejk_validation.pdf.gz | 908 KB | Display | wwPDB validaton report |
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Full document | 7ejk_full_validation.pdf.gz | 924.9 KB | Display | |
Data in XML | 7ejk_validation.xml.gz | 36.2 KB | Display | |
Data in CIF | 7ejk_validation.cif.gz | 54.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ej/7ejk ftp://data.pdbj.org/pub/pdb/validation_reports/ej/7ejk | HTTPS FTP |
-Related structure data
Related structure data | 31162MC 7ej0C 7ej8C 7ejaC 7el0 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, 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: Trichoplusia ni (cabbage looper) / 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.) 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 |
-Antibody / Protein / Non-polymers , 3 types, 3 molecules HR
#4: 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: Trichoplusia ni (cabbage looper) |
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#5: Protein | Mass: 50704.566 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ADRA2A, ADRA2R, ADRAR / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P08913 |
#6: Chemical | ChemComp-J5C / |
-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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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Specimen | Embedding applied: YES / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
EM embedding | Material: vitreous ice | ||||||||||||||||||||||||
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 / Nominal magnification: 105000 X / Nominal defocus max: 1400 nm / Nominal defocus min: 1000 nm / Calibrated defocus min: 800 nm / Calibrated defocus max: 2000 nm / Cs: 2.7 mm |
Image recording | Electron dose: 56 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 220513 / Symmetry type: POINT |