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Yorodumi- EMDB-22357: Structural Basis of the Activation of Heterotrimeric Gs-protein b... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-22357 | |||||||||
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Title | Structural Basis of the Activation of Heterotrimeric Gs-protein by Isoproterenol-bound Beta1-Adrenergic Receptor | |||||||||
Map data | Activation of Heterotrimeric Gs-protein by Isoproterenol-bound Beta1-Adrenergic Receptor | |||||||||
Sample |
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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 | single particle reconstruction / cryo EM / Resolution: 2.6 Å | |||||||||
Authors | Su M / Zhu L / Zhang Y / Paknejad N / Dey R / Huang J / Lee MY / Williams D / Jordan KD / Eng ET ...Su M / Zhu L / Zhang Y / Paknejad N / Dey R / Huang J / Lee MY / Williams D / Jordan KD / Eng ET / Ernst OP / Meyerson JR / Hite RK / Walz T / Liu W / Huang XY | |||||||||
Funding support | United States, 1 items
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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 | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_22357.map.gz | 477 MB | EMDB map data format | |
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Header (meta data) | emd-22357-v30.xml emd-22357.xml | 22.3 KB 22.3 KB | Display Display | EMDB header |
Images | emd_22357.png | 83.1 KB | ||
Others | emd_22357_additional.map.gz | 59.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22357 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22357 | HTTPS FTP |
-Validation report
Summary document | emd_22357_validation.pdf.gz | 323.4 KB | Display | EMDB validaton report |
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Full document | emd_22357_full_validation.pdf.gz | 322.9 KB | Display | |
Data in XML | emd_22357_validation.xml.gz | 8.1 KB | Display | |
Data in CIF | emd_22357_validation.cif.gz | 9.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22357 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22357 | HTTPS FTP |
-Related structure data
Related structure data | 7jjoMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_22357.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Activation of Heterotrimeric Gs-protein by Isoproterenol-bound Beta1-Adrenergic Receptor | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.532 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: low-pass filtered to 6 A map
File | emd_22357_additional.map | ||||||||||||
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Annotation | low-pass filtered to 6 A map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Isoproterenol bound beta1 adrenergic receptor in complex with het...
+Supramolecule #1: Isoproterenol bound beta1 adrenergic receptor in complex with het...
+Supramolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1,...
+Supramolecule #3: Nanobody 35
+Supramolecule #4: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Supramolecule #5: Beta1-Adrenergic Receptor
+Macromolecule #1: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #2: Nanobody 35
+Macromolecule #3: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #5: Beta1-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 | 1.5 mg/mL |
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Buffer | pH: 7 |
Grid | Model: Quantifoil / Material: GOLD / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 46.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 452312 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. v2) / Details: ab initio |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. v2) / Details: non-uniform refinement |