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- PDB-6d9h: Cryo-EM structure of the human adenosine A1 receptor-Gi2-protein ... -
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Basic information
Entry | Database: PDB / ID: 6d9h | ||||||
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Title | Cryo-EM structure of the human adenosine A1 receptor-Gi2-protein complex bound to its endogenous agonist | ||||||
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![]() | SIGNALING PROTEIN / membrane protein / active-state G protein-coupled receptor / adenosine A1 receptor | ||||||
Function / homology | ![]() positive regulation of nucleoside transport / negative regulation of neurotrophin production / regulation of glomerular filtration / negative regulation of circadian sleep/wake cycle, non-REM sleep / positive regulation of peptide secretion / negative regulation of mucus secretion / purine nucleoside binding / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / negative regulation of glutamate secretion / negative regulation of long-term synaptic depression ...positive regulation of nucleoside transport / negative regulation of neurotrophin production / regulation of glomerular filtration / negative regulation of circadian sleep/wake cycle, non-REM sleep / positive regulation of peptide secretion / negative regulation of mucus secretion / purine nucleoside binding / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / negative regulation of glutamate secretion / negative regulation of long-term synaptic depression / negative regulation of hormone secretion / Muscarinic acetylcholine receptors / positive regulation of lipid catabolic process / negative regulation of synaptic transmission, GABAergic / heterotrimeric G-protein binding / Adenosine P1 receptors / G protein-coupled acetylcholine receptor activity / mucus secretion / G protein-coupled adenosine receptor activity / regulation of respiratory gaseous exchange by nervous system process / negative regulation of leukocyte migration / regulation of presynaptic cytosolic calcium ion concentration / regulation of sensory perception of pain / G protein-coupled adenosine receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis / response to purine-containing compound / positive regulation of systemic arterial blood pressure / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / positive regulation of urine volume / positive regulation of potassium ion transport / negative regulation of adenylate cyclase activity / negative regulation of synaptic transmission, glutamatergic / positive regulation of neural precursor cell proliferation / G protein-coupled serotonin receptor activity / negative regulation of systemic arterial blood pressure / regulation of cardiac muscle cell contraction / gamma-aminobutyric acid signaling pathway / triglyceride homeostasis / negative regulation of synaptic transmission / protein targeting to membrane / long-term synaptic depression / regulation of locomotion / temperature homeostasis / leukocyte migration / presynaptic active zone / neuronal dense core vesicle / calyx of Held / detection of temperature stimulus involved in sensory perception of pain / regulation of calcium ion transport / negative regulation of acute inflammatory response / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / negative regulation of apoptotic signaling pathway / negative regulation of long-term synaptic potentiation / asymmetric synapse / axolemma / : / Adenylate cyclase inhibitory pathway / fatty acid homeostasis / negative regulation of lipid catabolic process / phagocytosis / lipid catabolic process / positive regulation of insulin receptor signaling pathway / positive regulation of protein dephosphorylation / positive regulation of vascular associated smooth muscle cell proliferation / heat shock protein binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / excitatory postsynaptic potential / response to nutrient / positive regulation of superoxide anion generation / Regulation of insulin secretion / G protein-coupled receptor binding / apoptotic signaling pathway / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / 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 / terminal bouton / 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 / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / 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 Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å | ||||||
![]() | Draper-Joyce, C.J. / Khoshouei, M. / Thal, D.M. / Liang, Y.-L. / Nguyen, A.T.N. / Furness, S.G.B. / Venugopal, H. / Baltos, J. / Plitzko, J.M. / Danev, R. ...Draper-Joyce, C.J. / Khoshouei, M. / Thal, D.M. / Liang, Y.-L. / Nguyen, A.T.N. / Furness, S.G.B. / Venugopal, H. / Baltos, J. / Plitzko, J.M. / Danev, R. / Baumeister, W. / May, L.T. / Wootten, D. / Sexton, P. / Glukhova, A. / Christopoulos, A. | ||||||
![]() | ![]() Title: Structure of the adenosine-bound human adenosine A receptor-G complex. Authors: Christopher J Draper-Joyce / Maryam Khoshouei / David M Thal / Yi-Lynn Liang / Anh T N Nguyen / Sebastian G B Furness / Hariprasad Venugopal / Jo-Anne Baltos / Jürgen M Plitzko / Radostin ...Authors: Christopher J Draper-Joyce / Maryam Khoshouei / David M Thal / Yi-Lynn Liang / Anh T N Nguyen / Sebastian G B Furness / Hariprasad Venugopal / Jo-Anne Baltos / Jürgen M Plitzko / Radostin Danev / Wolfgang Baumeister / Lauren T May / Denise Wootten / Patrick M Sexton / Alisa Glukhova / Arthur Christopoulos / ![]() ![]() ![]() ![]() Abstract: The class A adenosine A receptor (AR) is a G-protein-coupled receptor that preferentially couples to inhibitory G heterotrimeric G proteins, has been implicated in numerous diseases, yet remains ...The class A adenosine A receptor (AR) is a G-protein-coupled receptor that preferentially couples to inhibitory G heterotrimeric G proteins, has been implicated in numerous diseases, yet remains poorly targeted. Here we report the 3.6 Å structure of the human AR in complex with adenosine and heterotrimeric G protein determined by Volta phase plate cryo-electron microscopy. Compared to inactive AR, there is contraction at the extracellular surface in the orthosteric binding site mediated via movement of transmembrane domains 1 and 2. At the intracellular surface, the G protein engages the AR primarily via amino acids in the C terminus of the Gα α5-helix, concomitant with a 10.5 Å outward movement of the AR transmembrane domain 6. Comparison with the agonist-bound β adrenergic receptor-G-protein complex reveals distinct orientations for each G-protein subtype upon engagement with its receptor. This active AR structure provides molecular insights into receptor and G-protein selectivity. | ||||||
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 | ![]() | 170.7 KB | Display | ![]() |
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PDB format | ![]() | 134.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 761 KB | Display | ![]() |
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Full document | ![]() | 765.5 KB | Display | |
Data in XML | ![]() | 28.7 KB | Display | |
Data in CIF | ![]() | 42.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7835MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 40502.863 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Protein | Mass: 38534.062 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.) ![]() ![]() |
#4: Protein | Mass: 43537.309 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#5: Chemical | ChemComp-ADN / |
-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: Human adenosine A1 receptor-Gi2-protein complex bound to its endogenous agonist adenosine Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE-PROPANE / Humidity: 100 % / Chamber temperature: 277 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 / Calibrated magnification: 47170 X / C2 aperture diameter: 50 µm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 8 sec. / Electron dose: 50 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
EM imaging optics | Phase plate: The images were taken at 500 defocus |
Image scans | Width: 3838 / Height: 3710 / Movie frames/image: 50 |
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Processing
Software | Name: PHENIX / Version: 1.12_2829: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Details: Phase plate CTF correction / Type: NONE | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 263321 / Symmetry type: POINT | ||||||||||||||||||||||||
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