+Open data
-Basic information
Entry | Database: PDB / ID: 7xjh | ||||||
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Title | Isoproterenol-activated dog beta3 adrenergic receptor | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / GPCR | ||||||
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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
Authors | Shihoya, W. / Nureki, O. | ||||||
Funding support | Japan, 1items
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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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7xjh.cif.gz | 190.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7xjh.ent.gz | 147.5 KB | Display | PDB format |
PDBx/mmJSON format | 7xjh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7xjh_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 7xjh_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 7xjh_validation.xml.gz | 39 KB | Display | |
Data in CIF | 7xjh_validation.cif.gz | 58.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xj/7xjh ftp://data.pdbj.org/pub/pdb/validation_reports/xj/7xjh | HTTPS FTP |
-Related structure data
Related structure data | 33227MC 7dh5C M: map data used to model this data C: citing same article (ref.) |
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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: 44255.664 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAS, GNAS1, GSP / Production host: Baculovirus expression vector pFastBac1-HM / References: UniProt: P63092 |
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#2: Protein | Mass: 37784.301 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Gnb1 / Production host: Baculovirus expression vector pFastBac1-HM / References: UniProt: P54311 |
#3: Protein | Mass: 7547.685 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: GNG2 / Production host: Baculovirus expression vector pFastBac1-HM / References: UniProt: P63212 |
-Antibody / Protein / Non-polymers , 3 types, 3 molecules NR
#4: Antibody | Mass: 15015.728 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) unidentified (others) / Production host: Escherichia coli (E. coli) |
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#5: Protein | Mass: 42441.293 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Canis lupus familiaris (dog) / Gene: ADRB3, B3AR / Production host: Baculovirus expression vector pFastBac1-HM / References: UniProt: O02662 |
#6: Chemical | ChemComp-5FW / |
-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
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 8 | ||||||||||||||||||||||||||||||||||||||||||
Specimen | Conc.: 7 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||||||||||||||
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 defocus max: 2500 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.19_4092: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 104835 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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