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- PDB-9l84: Structure of beta1-AR-Gs complex bound to epinephrine and an allo... -

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Entry
Database: PDB / ID: 9l84
TitleStructure of beta1-AR-Gs complex bound to epinephrine and an allosteric modulator
Components
  • (Guanine nucleotide-binding protein ...) x 3
  • Beta-1 adrenergic receptor
  • NB35
KeywordsMEMBRANE PROTEIN / GPCR
Function / homology
Function and homology information


beta-adrenergic receptor activity / positive regulation of heart rate by epinephrine-norepinephrine / positive regulation of the force of heart contraction by epinephrine-norepinephrine / beta1-adrenergic receptor activity / G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / alpha-2A adrenergic receptor binding / regulation of circadian sleep/wake cycle, sleep / sensory perception of chemical stimulus / fear response / mu-type opioid receptor binding ...beta-adrenergic receptor activity / positive regulation of heart rate by epinephrine-norepinephrine / positive regulation of the force of heart contraction by epinephrine-norepinephrine / beta1-adrenergic receptor activity / G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / alpha-2A adrenergic receptor binding / regulation of circadian sleep/wake cycle, sleep / sensory perception of chemical stimulus / fear response / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 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 / Ca2+ pathway / G alpha (z) signalling events / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure / heat generation / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / Adrenoceptors / beta-2 adrenergic receptor binding / G alpha (i) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / 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 / G alpha (12/13) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / negative regulation of multicellular organism growth / Ca2+ pathway / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (z) signalling events / Extra-nuclear estrogen signaling / photoreceptor outer segment membrane / G alpha (s) signalling events / G alpha (q) signalling events / spectrin binding / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / diet induced thermogenesis / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Vasopressin regulates renal water homeostasis via Aquaporins / alkylglycerophosphoethanolamine phosphodiesterase activity / photoreceptor outer segment / D1 dopamine receptor binding / neuronal dense core vesicle / brown fat cell differentiation / adenylate cyclase-activating adrenergic receptor signaling pathway / insulin-like growth factor receptor binding / cardiac muscle cell apoptotic process / ionotropic glutamate receptor binding / photoreceptor inner segment / response to cold / adenylate cyclase activator activity / PDZ domain binding / Schaffer collateral - CA1 synapse / G-protein beta/gamma-subunit complex binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / cellular response to catecholamine stimulus / adenylate cyclase-activating dopamine receptor signaling pathway / G-protein beta-subunit binding / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / sensory perception of taste / positive regulation of cold-induced thermogenesis / signaling receptor complex adaptor activity / positive regulation of cytosolic calcium ion concentration / retina development in camera-type eye / cell body / GTPase binding / G alpha (s) signalling events / cellular response to hypoxia / phospholipase C-activating G protein-coupled receptor signaling pathway / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / early endosome / cell population proliferation / positive regulation of MAPK cascade
Similarity search - Function
Beta 1 adrenoceptor / Adrenoceptor family / G-protein alpha subunit, group S / Serpentine type 7TM GPCR chemoreceptor Srsx / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / G-protein, gamma subunit ...Beta 1 adrenoceptor / Adrenoceptor family / G-protein alpha subunit, group S / Serpentine type 7TM GPCR chemoreceptor Srsx / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / G protein beta WD-40 repeat protein / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
L-EPINEPHRINE / Chem-DR7 / Guanine nucleotide-binding protein G(s) subunit alpha isoforms short / Beta-1 adrenergic receptor / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Similarity search - Component
Biological speciesBos taurus (domestic cattle)
Rattus norvegicus (Norway rat)
Lama glama (llama)
Homo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.22 Å
AuthorsSun, Q. / He, G. / Xu, X. / Liu, X.
Funding support China, 2items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32122041 China
National Natural Science Foundation of China (NSFC)32100968 China
CitationJournal: To Be Published
Title: Structure of beta1-AR-Gs complex bound to epinephrine and an allosteric modulator
Authors: Sun, Q. / He, G. / Xu, X. / Liu, X.
History
DepositionDec 27, 2024Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Dec 31, 2025Provider: repository / Type: Initial release
Revision 1.0Dec 31, 2025Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Dec 31, 2025Data content type: Additional map / Part number: 1 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0Dec 31, 2025Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Dec 31, 2025Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Dec 31, 2025Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Dec 31, 2025Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
B: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
G: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
N: NB35
R: Beta-1 adrenergic receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)159,3827
Polymers158,4945
Non-polymers8882
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG

#1: Protein Guanine nucleotide-binding protein G(s) subunit alpha isoforms short / Adenylate cyclase-stimulating G alpha protein


Mass: 45769.527 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Bos taurus (domestic cattle) / Gene: GNAS, GNAS1 / Production host: Trichoplusia ni (cabbage looper)
References: UniProt: P04896, Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement
#2: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 38744.371 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Gnb1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P54311
#3: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / G gamma-I


Mass: 7563.750 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Bos taurus (domestic cattle) / Gene: GNG2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P63212

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Antibody / Protein , 2 types, 2 molecules NR

#4: Antibody NB35


Mass: 15140.742 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Lama glama (llama) / Production host: Escherichia coli (E. coli)
#5: Protein Beta-1 adrenergic receptor / Beta-1 adrenoreceptor / Beta-1 adrenoceptor


Mass: 51275.547 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ADRB1, ADRB1R, B1AR / Production host: Homo sapiens (human) / References: UniProt: P08588

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Non-polymers , 2 types, 2 molecules

#6: Chemical ChemComp-DR7 / (3S,8S,9S,12S)-3,12-BIS(1,1-DIMETHYLETHYL)-8-HYDROXY-4,11-DIOXO-9-(PHENYLMETHYL)-6-[[4-(2-PYRIDINYL)PHENYL]METHYL]-2,5, 6,10,13-PENTAAZATETRADECANEDIOIC ACID DIMETHYL ESTER / ATAZANAVIR / METHYL [(1S,4S,5S,10S)-4-BENZYL-1,10-DI-TERT-BUTYL-5-HYDROXY-2,9,12-TRIOXO-7-(4-PYRIDIN-2-YLBENZYL)-13-OXA-3,7,8,11-TETRAAZATET RADEC-1-YL]CARBAMATE


Mass: 704.855 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C38H52N6O7 / Feature type: SUBJECT OF INVESTIGATION
#7: Chemical ChemComp-ALE / L-EPINEPHRINE / ADRENALINE


Mass: 183.204 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C9H13NO3 / Feature type: SUBJECT OF INVESTIGATION

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Details

Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Structure of beta1-AR-Gs complex bound to epinephrine and an allosteric modulator
Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1600 nm / Nominal defocus min: 1300 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

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Processing

CTF correctionType: NONE
3D reconstructionResolution: 3.22 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 146161 / Symmetry type: POINT

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