+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33227 | |||||||||
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Title | Isoproterenol-activated dog beta3 adrenergic receptor | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information beta3-adrenergic receptor activity / beta-adrenergic receptor activity / epinephrine binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / serotonin binding / 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 ...beta3-adrenergic receptor activity / beta-adrenergic receptor activity / epinephrine binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / serotonin binding / 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 / G protein-coupled serotonin receptor activity / 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 / norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure / 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 / neurotransmitter receptor activity / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / PKA activation in glucagon signalling / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / hair follicle placode formation / photoreceptor outer segment / developmental growth / D1 dopamine receptor binding / intracellular transport / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / cardiac muscle cell apoptotic process / adenylate cyclase activator activity / photoreceptor inner segment / trans-Golgi network membrane / G-protein beta/gamma-subunit complex binding / bone development / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / cognition / platelet aggregation / 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 / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / GPER1 signaling / G-protein beta-subunit binding / heterotrimeric G-protein complex / sensory perception of smell / signaling receptor complex adaptor activity / GTPase binding / retina development in camera-type eye / cellular response to hypoxia / positive regulation of cold-induced thermogenesis / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / cell body / G alpha (s) signalling events / chemical synaptic transmission Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Rattus norvegicus (Norway rat) / Bos taurus (cattle) / unidentified (others) / Canis lupus familiaris (dog) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Shihoya W / Nureki O | |||||||||
Funding support | Japan, 1 items
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Citation | Journal: Mol Cell / Year: 2021 Title: Cryo-EM structure of the β3-adrenergic receptor reveals the molecular basis of subtype selectivity. Authors: Chisae Nagiri / Kazuhiro Kobayashi / Atsuhiro Tomita / Masahiko Kato / Kan Kobayashi / Keitaro Yamashita / Tomohiro Nishizawa / Asuka Inoue / Wataru Shihoya / Osamu Nureki / Abstract: The β-adrenergic receptor (βAR) is predominantly expressed in adipose tissue and urinary bladder and has emerged as an attractive drug target for the treatment of type 2 diabetes, obesity, and ...The β-adrenergic receptor (βAR) is predominantly expressed in adipose tissue and urinary bladder and has emerged as an attractive drug target for the treatment of type 2 diabetes, obesity, and overactive bladder (OAB). Here, we report the cryogenic electron microscopy structure of the βAR-G signaling complex with the selective agonist mirabegron, a first-in-class drug for OAB. Comparison of this structure with the previously reported βAR and βAR structures reveals a receptor activation mechanism upon mirabegron binding to the orthosteric site. Notably, the narrower exosite in βAR creates a perpendicular pocket for mirabegron. Mutational analyses suggest that a combination of both the exosite shape and the amino-acid-residue substitutions defines the drug selectivity of the βAR agonists. Our findings provide a molecular basis for βAR subtype selectivity, allowing the design of more-selective agents with fewer adverse effects. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_33227.map.gz | 2.3 MB | EMDB map data format | |
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Header (meta data) | emd-33227-v30.xml emd-33227.xml | 23 KB 23 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_33227_fsc.xml | 6.9 KB | Display | FSC data file |
Images | emd_33227.png | 115.3 KB | ||
Masks | emd_33227_msk_1.map | 12.4 MB | Mask map | |
Others | emd_33227_half_map_1.map.gz emd_33227_half_map_2.map.gz | 11.2 MB 11.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33227 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33227 | HTTPS FTP |
-Validation report
Summary document | emd_33227_validation.pdf.gz | 595.5 KB | Display | EMDB validaton report |
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Full document | emd_33227_full_validation.pdf.gz | 595.1 KB | Display | |
Data in XML | emd_33227_validation.xml.gz | 12.6 KB | Display | |
Data in CIF | emd_33227_validation.cif.gz | 16.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33227 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33227 | HTTPS FTP |
-Related structure data
Related structure data | 7xjhMC 7dh5C 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_33227.map.gz / Format: CCP4 / Size: 12.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.09526 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_33227_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_33227_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_33227_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Dog beta3 adrenergic receptor bound to mirabegron in complex with...
+Supramolecule #1: Dog beta3 adrenergic receptor bound to mirabegron in complex with...
+Supramolecule #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Supramolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Supramolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Supramolecule #5: nanobody Nb35
+Supramolecule #6: Beta-3 adrenergic receptor
+Macromolecule #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #4: Nanobody-35
+Macromolecule #5: Beta-3 adrenergic receptor
+Macromolecule #6: ISOPRENALINE
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 7 mg/mL |
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Buffer | pH: 8 |
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: 2.5 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |