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Yorodumi- PDB-7jjo: Structural Basis of the Activation of Heterotrimeric Gs-protein b... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7jjo | ||||||
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Title | Structural Basis of the Activation of Heterotrimeric Gs-protein by Isoproterenol-bound Beta1-Adrenergic Receptor | ||||||
Components |
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Keywords | SIGNALING PROTEIN / Gs protein / GPCR-Gs complex / Agonist | ||||||
Function / homology | Function and homology information beta1-adrenergic receptor activity / positive regulation of heart rate by epinephrine-norepinephrine / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / regulation of circadian sleep/wake cycle, sleep / sensory perception of chemical stimulus / mu-type opioid receptor binding / Activation of the phototransduction cascade / corticotropin-releasing hormone receptor 1 binding ...beta1-adrenergic receptor activity / positive regulation of heart rate by epinephrine-norepinephrine / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / regulation of circadian sleep/wake cycle, sleep / sensory perception of chemical stimulus / mu-type opioid receptor binding / Activation of the phototransduction cascade / corticotropin-releasing hormone receptor 1 binding / D1 dopamine receptor binding / norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure / 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 / G alpha (12/13) signalling events / 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 / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / beta-2 adrenergic receptor binding / Extra-nuclear estrogen signaling / G alpha (z) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / adenylate cyclase-activating adrenergic receptor signaling pathway / adenylate cyclase activator activity / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / G-protein beta/gamma-subunit complex binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / photoreceptor disc membrane / cellular response to catecholamine stimulus / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / early endosome / G protein-coupled receptor signaling pathway / GTPase activity / GTP binding / identical protein binding / membrane / metal ion binding / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Bos taurus (cattle) Lama glama (llama) Meleagris gallopavo (turkey) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.6 Å | ||||||
Authors | Su, M. / Zhu, L. / Zhang, Y. / Paknejad, N. / Dey, R. / Huang, J. / Lee, M.Y. / Williams, D. / Jordan, K.D. / Eng, E.T. ...Su, M. / Zhu, L. / Zhang, Y. / Paknejad, N. / Dey, R. / Huang, J. / Lee, M.Y. / Williams, D. / Jordan, K.D. / Eng, E.T. / Ernst, O.P. / Meyerson, J.R. / Hite, R.K. / Walz, T. / Liu, W. / Huang, X.Y. | ||||||
Funding support | United States, 1items
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Citation | Journal: Mol Cell / Year: 2020 Title: Structural Basis of the Activation of Heterotrimeric Gs-Protein by Isoproterenol-Bound β-Adrenergic Receptor. Authors: Minfei Su / Lan Zhu / Yixiao Zhang / Navid Paknejad / Raja Dey / Jianyun Huang / Ming-Yue Lee / Dewight Williams / Kelsey D Jordan / Edward T Eng / Oliver P Ernst / Joel R Meyerson / Richard ...Authors: Minfei Su / Lan Zhu / Yixiao Zhang / Navid Paknejad / Raja Dey / Jianyun Huang / Ming-Yue Lee / Dewight Williams / Kelsey D Jordan / Edward T Eng / Oliver P Ernst / Joel R Meyerson / Richard K Hite / Thomas Walz / Wei Liu / Xin-Yun Huang / Abstract: Cardiac disease remains the leading cause of morbidity and mortality worldwide. The β-adrenergic receptor (β-AR) is a major regulator of cardiac functions and is downregulated in the majority of ...Cardiac disease remains the leading cause of morbidity and mortality worldwide. The β-adrenergic receptor (β-AR) is a major regulator of cardiac functions and is downregulated in the majority of heart failure cases. A key physiological process is the activation of heterotrimeric G-protein Gs by β-ARs, leading to increased heart rate and contractility. Here, we use cryo-electron microscopy and functional studies to investigate the molecular mechanism by which β-AR activates Gs. We find that the tilting of α5-helix breaks a hydrogen bond between the sidechain of His373 in the C-terminal α5-helix and the backbone carbonyl of Arg38 in the N-terminal αN-helix of Gα. Together with the disruption of another interacting network involving Gln59 in the α1-helix, Ala352 in the β6-α5 loop, and Thr355 in the α5-helix, these conformational changes might lead to the deformation of the GDP-binding pocket. Our data provide molecular insights into the activation of G-proteins by G-protein-coupled receptors. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7jjo.cif.gz | 338.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7jjo.ent.gz | 280.3 KB | Display | PDB format |
PDBx/mmJSON format | 7jjo.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7jjo_validation.pdf.gz | 716.3 KB | Display | wwPDB validaton report |
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Full document | 7jjo_full_validation.pdf.gz | 721.6 KB | Display | |
Data in XML | 7jjo_validation.xml.gz | 32.5 KB | Display | |
Data in CIF | 7jjo_validation.cif.gz | 48.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jj/7jjo ftp://data.pdbj.org/pub/pdb/validation_reports/jj/7jjo | HTTPS FTP |
-Related structure data
Related structure data | 22357MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules BAG
#1: Protein | Mass: 37285.734 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: GNB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P62871 |
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#3: Protein | Mass: 44694.551 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: GNAS, GNAS1 / Production host: Escherichia coli (E. coli) / References: UniProt: P04896 |
#4: Protein | Mass: 7845.078 Da / Num. of mol.: 1 / Mutation: C68S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63212 |
-Antibody / Protein / Non-polymers , 3 types, 3 molecules NR
#2: Antibody | 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) |
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#5: Protein | Mass: 57958.668 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Meleagris gallopavo (turkey) / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P07700*PLUS |
#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
Component |
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Molecular weight | Value: 0.16 MDa / Experimental value: NO | ||||||||||||||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7 | ||||||||||||||||||||||||||||||||||||
Specimen | Conc.: 1.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil | ||||||||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-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 |
Image recording | Electron dose: 46 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||
3D reconstruction | Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 452312 / Symmetry type: POINT |