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- PDB-6gdg: Cryo-EM structure of the adenosine A2A receptor bound to a miniGs... -
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Basic information
Entry | Database: PDB / ID: 6gdg | |||||||||
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Title | Cryo-EM structure of the adenosine A2A receptor bound to a miniGs heterotrimer | |||||||||
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![]() | MEMBRANE PROTEIN / G-protein coupled receptor / adenosine / GPCR / A2A receptor | |||||||||
Function / homology | ![]() positive regulation of acetylcholine secretion, neurotransmission / positive regulation of circadian sleep/wake cycle, sleep / regulation of norepinephrine secretion / negative regulation of alpha-beta T cell activation / Adenosine P1 receptors / G protein-coupled adenosine receptor activity / G protein-coupled adenosine receptor signaling pathway / response to purine-containing compound / sensory perception / positive regulation of urine volume ...positive regulation of acetylcholine secretion, neurotransmission / positive regulation of circadian sleep/wake cycle, sleep / regulation of norepinephrine secretion / negative regulation of alpha-beta T cell activation / Adenosine P1 receptors / G protein-coupled adenosine receptor activity / G protein-coupled adenosine receptor signaling pathway / response to purine-containing compound / sensory perception / positive regulation of urine volume / NGF-independant TRKA activation / Surfactant metabolism / synaptic transmission, dopaminergic / : / inhibitory postsynaptic potential / negative regulation of vascular permeability / synaptic transmission, cholinergic / type 5 metabotropic glutamate receptor binding / positive regulation of glutamate secretion / blood circulation / response to caffeine / intermediate filament / eating behavior / DNA polymerase processivity factor activity / presynaptic active zone / alpha-actinin binding / membrane depolarization / regulation of calcium ion transport / PKA activation in glucagon signalling / hair follicle placode formation / asymmetric synapse / protein-disulfide reductase activity / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / axolemma / : / intracellular transport / D1 dopamine receptor binding / Hedgehog 'off' state / cellular defense response / prepulse inhibition / phagocytosis / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / response to amphetamine / activation of adenylate cyclase activity / adenylate cyclase activator activity / presynaptic modulation of chemical synaptic transmission / excitatory postsynaptic potential / positive regulation of synaptic transmission, glutamatergic / neuron projection morphogenesis / trans-Golgi network membrane / regulation of mitochondrial membrane potential / cell redox homeostasis / synaptic transmission, glutamatergic / positive regulation of long-term synaptic potentiation / locomotory behavior / central nervous system development / astrocyte activation / positive regulation of synaptic transmission, GABAergic / positive regulation of protein secretion / apoptotic signaling pathway / positive regulation of apoptotic signaling pathway / ionotropic glutamate receptor binding / insulin-like growth factor receptor binding / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / bone development / Activation of the phototransduction cascade / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / negative regulation of inflammatory response / 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 Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.11 Å | |||||||||
![]() | Garcia-Nafria, J. / Lee, Y. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM structure of the adenosine A receptor coupled to an engineered heterotrimeric G protein. Authors: Javier García-Nafría / Yang Lee / Xiaochen Bai / Byron Carpenter / Christopher G Tate / ![]() Abstract: The adenosine A receptor (AR) is a prototypical G protein-coupled receptor (GPCR) that couples to the heterotrimeric G protein G. Here, we determine the structure by electron cryo-microscopy (cryo-EM) ...The adenosine A receptor (AR) is a prototypical G protein-coupled receptor (GPCR) that couples to the heterotrimeric G protein G. Here, we determine the structure by electron cryo-microscopy (cryo-EM) of AR at pH 7.5 bound to the small molecule agonist NECA and coupled to an engineered heterotrimeric G protein, which contains mini-G, the βγ subunits and nanobody Nb35. Most regions of the complex have a resolution of ~3.8 Å or better. Comparison with the 3.4 Å resolution crystal structure shows that the receptor and mini-G are virtually identical and that the density of the side chains and ligand are of comparable quality. However, the cryo-EM density map also indicates regions that are flexible in comparison to the crystal structures, which unexpectedly includes regions in the ligand binding pocket. In addition, an interaction between intracellular loop 1 of the receptor and the β subunit of the G protein was observed. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 205.2 KB | Display | ![]() |
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PDB format | ![]() | 158.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 811.1 KB | Display | ![]() |
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Full document | ![]() | 812 KB | Display | |
Data in XML | ![]() | 30 KB | Display | |
Data in CIF | ![]() | 45.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 4390MC M: map data used to model this data C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data size: 1.1 TB Data #1: Unaligned multi-frame micrographs [micrographs - multiframe] Data #2: Micelle subtracted particles [picked particles - multiframe - processed] Data #3: Particles before subtraction [picked particles - multiframe - processed]) |
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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 BCD
#2: Protein | Mass: 37285.734 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#3: Protein | Mass: 7845.078 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#4: Protein | Mass: 28907.684 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Protein / Antibody / Non-polymers , 3 types, 3 molecules AE![](data/chem/img/NEC.gif)
![](data/chem/img/NEC.gif)
#1: Protein | Mass: 52909.785 Da / Num. of mol.: 1 / Fragment: UNP residues 37-144,UNP residues 8-316 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: trxA, ADORA2A, ADORA2 / Production host: ![]() References: UniProt: Q14F07, UniProt: P29274, UniProt: P0AA25*PLUS |
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#5: Antibody | Mass: 16926.076 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
#6: Chemical | ChemComp-NEC / |
-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 |
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Molecular weight | Value: 0.137 MDa / Experimental value: NO | ||||||||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K |
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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 / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 60 sec. / Electron dose: 30 e/Å2 / Detector mode: COUNTING / Film or detector model: FEI FALCON III (4k x 4k) |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.11 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 128002 / Algorithm: FOURIER SPACE / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: RECIPROCAL |