+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-37985 | |||||||||
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Title | Cryo-EM structure of adenosine receptor A3AR bound to CF101 | |||||||||
Map data | ||||||||||
Sample |
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Keywords | GPCR / adenosine A3 receptor / ligand selectivity / CF101 / MEMBRANE PROTEIN / MEMBRANE PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | Function and homology information Adenylate cyclase inhibitory pathway / regulation of norepinephrine secretion / Adenosine P1 receptors / G protein-coupled adenosine receptor activity / G protein-coupled adenosine receptor signaling pathway / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste ...Adenylate cyclase inhibitory pathway / regulation of norepinephrine secretion / Adenosine P1 receptors / G protein-coupled adenosine receptor activity / G protein-coupled adenosine receptor signaling pathway / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / alkylglycerophosphoethanolamine phosphodiesterase activity / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / G alpha (i) signalling events / regulation of heart contraction / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / negative regulation of NF-kappaB transcription factor activity / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / photoreceptor outer segment / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / G protein-coupled serotonin receptor binding / activation of adenylate cyclase activity / regulation of mitotic spindle organization / cellular response to forskolin / cardiac muscle cell apoptotic process / presynaptic modulation of chemical synaptic transmission / photoreceptor inner segment / negative regulation of cell migration / G protein-coupled receptor binding / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Schaffer collateral - CA1 synapse / response to wounding / cellular response to catecholamine stimulus / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / GDP binding / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / GTPase binding / retina development in camera-type eye / cellular response to hypoxia / presynaptic membrane / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / cell cortex / midbody / G alpha (i) signalling events / cell body / cell population proliferation / inflammatory response / G protein-coupled receptor signaling pathway / cell division / negative regulation of cell population proliferation / GTPase activity / centrosome / synapse / dendrite / protein-containing complex binding / GTP binding / magnesium ion binding Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Bos taurus (cattle) / Rattus norvegicus (Norway rat) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.29 Å | |||||||||
Authors | Cai H / Xu Y / Xu HE | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nat Commun / Year: 2024 Title: Cryo-EM structures of adenosine receptor AAR bound to selective agonists. Authors: Hongmin Cai / Shimeng Guo / Youwei Xu / Jun Sun / Junrui Li / Zhikan Xia / Yi Jiang / Xin Xie / H Eric Xu / Abstract: The adenosine A receptor (AAR), a key member of the G protein-coupled receptor family, is a promising therapeutic target for inflammatory and cancerous conditions. The selective AAR agonists, CF101 ...The adenosine A receptor (AAR), a key member of the G protein-coupled receptor family, is a promising therapeutic target for inflammatory and cancerous conditions. The selective AAR agonists, CF101 and CF102, are clinically significant, yet their recognition mechanisms remained elusive. Here we report the cryogenic electron microscopy structures of the full-length human AAR bound to CF101 and CF102 with heterotrimeric G protein in complex at 3.3-3.2 Å resolution. These agonists reside in the orthosteric pocket, forming conserved interactions via their adenine moieties, while their 3-iodobenzyl groups exhibit distinct orientations. Functional assays reveal the critical role of extracellular loop 3 in AAR's ligand selectivity and receptor activation. Key mutations, including His, Ser, and Ser, in a unique sub-pocket of AAR, significantly impact receptor activation. Comparative analysis with the inactive AAR structure highlights a conserved receptor activation mechanism. Our findings provide comprehensive insights into the molecular recognition and signaling of AAR, paving the way for designing subtype-selective adenosine receptor ligands. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_37985.map.gz | 59.8 MB | EMDB map data format | |
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Header (meta data) | emd-37985-v30.xml emd-37985.xml | 20.9 KB 20.9 KB | Display Display | EMDB header |
Images | emd_37985.png | 40.1 KB | ||
Filedesc metadata | emd-37985.cif.gz | 6.3 KB | ||
Others | emd_37985_half_map_1.map.gz emd_37985_half_map_2.map.gz | 59.5 MB 59.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-37985 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-37985 | HTTPS FTP |
-Validation report
Summary document | emd_37985_validation.pdf.gz | 831.2 KB | Display | EMDB validaton report |
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Full document | emd_37985_full_validation.pdf.gz | 830.8 KB | Display | |
Data in XML | emd_37985_validation.xml.gz | 12.4 KB | Display | |
Data in CIF | emd_37985_validation.cif.gz | 14.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37985 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37985 | HTTPS FTP |
-Related structure data
Related structure data | 8x16MC 8x17C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_37985.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.824 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_37985_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_37985_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Cryo-EM structure of adenosine receptor A3AR bound to CF101
+Supramolecule #1: Cryo-EM structure of adenosine receptor A3AR bound to CF101
+Supramolecule #2: A3AR
+Supramolecule #3: G protein
+Supramolecule #4: G protein
+Supramolecule #5: scFV16
+Macromolecule #1: Adenosine receptor A3
+Macromolecule #2: Guanine nucleotide-binding protein G(i) subunit alpha-1
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #5: scFv16
+Macromolecule #6: Piclidenoson
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 5.0 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.29 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 271323 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |