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- PDB-7na7: Structures of human ghrelin receptor-Gi complexes with ghrelin an... -
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Basic information
Entry | Database: PDB / ID: 7na7 | |||||||||
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Title | Structures of human ghrelin receptor-Gi complexes with ghrelin and a synthetic agonist | |||||||||
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![]() | MEMBRANE PROTEIN / GPCR / appetite / energy homeostasis / reward signaling | |||||||||
Function / homology | ![]() positive regulation of bone development / positive regulation of gastric mucosal blood circulation / ghrelin receptor binding / negative regulation of locomotion / cortisol secretion / growth hormone secretagogue receptor activity / regulation of hindgut contraction / growth hormone-releasing hormone activity / negative regulation of circadian sleep/wake cycle, REM sleep / regulation of growth hormone secretion ...positive regulation of bone development / positive regulation of gastric mucosal blood circulation / ghrelin receptor binding / negative regulation of locomotion / cortisol secretion / growth hormone secretagogue receptor activity / regulation of hindgut contraction / growth hormone-releasing hormone activity / negative regulation of circadian sleep/wake cycle, REM sleep / regulation of growth hormone secretion / positive regulation of small intestinal transit / regulation of response to food / negative regulation of locomotion involved in locomotory behavior / growth hormone-releasing hormone receptor activity / regulation of gastric motility / response to follicle-stimulating hormone / regulation of transmission of nerve impulse / positive regulation of circadian sleep/wake cycle, non-REM sleep / positive regulation of cortisol secretion / positive regulation of corticotropin secretion / positive regulation of growth rate / ghrelin secretion / neuronal dense core vesicle lumen / gastric acid secretion / positive regulation of appetite / growth hormone secretion / negative regulation of norepinephrine secretion / positive regulation of small intestine smooth muscle contraction / negative regulation of macrophage apoptotic process / positive regulation of eating behavior / positive regulation of growth hormone secretion / adult feeding behavior / positive regulation of growth hormone receptor signaling pathway / negative regulation of appetite / actin polymerization or depolymerization / positive regulation of multicellular organism growth / cellular response to thyroid hormone stimulus / cartilage development / response to growth hormone / regulation of postsynapse organization / positive regulation of insulin-like growth factor receptor signaling pathway / positive regulation of synapse assembly / positive regulation of vascular endothelial cell proliferation / response to L-glutamate / negative regulation of interleukin-1 beta production / cellular response to insulin-like growth factor stimulus / response to food / positive regulation of fatty acid metabolic process / response to dexamethasone / regulation of synapse assembly / positive regulation of sprouting angiogenesis / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / negative regulation of endothelial cell proliferation / dendrite development / negative regulation of interleukin-6 production / peptide hormone binding / protein tyrosine kinase activator activity / decidualization / negative regulation of tumor necrosis factor production / response to electrical stimulus / Synthesis, secretion, and deacylation of Ghrelin / postsynaptic modulation of chemical synaptic transmission / positive regulation of insulin secretion involved in cellular response to glucose stimulus / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration / Adenylate cyclase inhibitory pathway / synapse assembly / response to hormone / D2 dopamine receptor binding / response to prostaglandin E / hormone-mediated signaling pathway / positive regulation of adipose tissue development / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / cellular response to forskolin / insulin-like growth factor receptor signaling pathway / regulation of mitotic spindle organization / negative regulation of angiogenesis / Peptide ligand-binding receptors / excitatory postsynaptic potential / Regulation of insulin secretion / synaptic membrane / positive regulation of cholesterol biosynthetic process / G protein-coupled receptor binding / negative regulation of insulin secretion / G protein-coupled receptor activity / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / positive regulation of insulin secretion / response to peptide hormone / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / negative regulation of inflammatory response / centriolar satellite / G-protein beta/gamma-subunit complex binding / response to estrogen / Schaffer collateral - CA1 synapse / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.7 Å | |||||||||
![]() | Liu, H. / Sun, D. / Sun, J. / Zhang, C. | |||||||||
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![]() | ![]() Title: Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren. Authors: Heng Liu / Dapeng Sun / Alexander Myasnikov / Marjorie Damian / Jean-Louis Baneres / Ji Sun / Cheng Zhang / ![]() ![]() Abstract: The hunger hormone ghrelin activates the ghrelin receptor GHSR to stimulate food intake and growth hormone secretion and regulate reward signaling. Acylation of ghrelin at Ser3 is required for its ...The hunger hormone ghrelin activates the ghrelin receptor GHSR to stimulate food intake and growth hormone secretion and regulate reward signaling. Acylation of ghrelin at Ser3 is required for its agonistic action on GHSR. Synthetic agonists of GHSR are under clinical evaluation for disorders related to appetite and growth hormone dysregulation. Here, we report high-resolution cryo-EM structures of the GHSR-G signaling complex with ghrelin and the non-peptide agonist ibutamoren as an investigational new drug. Our structures together with mutagenesis data reveal the molecular basis for the binding of ghrelin and ibutamoren. Structural comparison suggests a salt bridge and an aromatic cluster near the agonist-binding pocket as important structural motifs in receptor activation. Notable structural variations of the G and GHSR coupling are observed in our cryo-EM analysis. Our results provide a framework for understanding GHSR signaling and developing new GHSR agonist drugs. | |||||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 209.6 KB | Display | ![]() |
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PDB format | ![]() | 170.8 KB | Display | ![]() |
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-Validation report
Summary document | ![]() | 801.2 KB | Display | ![]() |
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Full document | ![]() | 810.5 KB | Display | |
Data in XML | ![]() | 36.6 KB | Display | |
Data in CIF | ![]() | 56.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 24267MC ![]() 7na8C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG
#1: Protein | Mass: 40429.059 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: Insect expression vector pBlueBacmsGCA1His (others) References: UniProt: P63096 |
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#2: Protein | Mass: 37417.918 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: Insect expression vector pBlueBacmsGCA1His (others) References: UniProt: P62873 |
#3: Protein | Mass: 7859.173 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: Insect expression vector pBlueBacmsGCA1His (others) References: UniProt: P59768 |
-Antibody / Protein / Protein/peptide / Non-polymers , 4 types, 5 molecules NRL

#4: Antibody | Mass: 26236.244 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Production host: Insect expression vector pBlueBacmsGCA1His (others) |
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#5: Protein | Mass: 41406.410 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: Insect expression vector pBlueBacmsGCA1His (others) References: UniProt: Q92847 |
#6: Protein/peptide | Mass: 1471.657 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
#7: Chemical |
-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 |
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Sample preparation
Component | Name: Complex of GHSR-Gi-ghrelin / Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: Insect expression vector pBlueBacmsGCA1His (others) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 82 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 280046 / Symmetry type: POINT |