+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31500 | |||||||||
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Title | ghrelin-bound ghrelin receptor in complex with Gq | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information ghrelin receptor binding / positive regulation of bone development / positive regulation of gastric mucosal blood circulation / negative regulation of locomotion / cortisol secretion / positive regulation of small intestinal transit / growth hormone-releasing hormone activity / negative regulation of circadian sleep/wake cycle, REM sleep / positive regulation of circadian sleep/wake cycle, non-REM sleep / regulation of response to food ...ghrelin receptor binding / positive regulation of bone development / positive regulation of gastric mucosal blood circulation / negative regulation of locomotion / cortisol secretion / positive regulation of small intestinal transit / growth hormone-releasing hormone activity / negative regulation of circadian sleep/wake cycle, REM sleep / positive regulation of circadian sleep/wake cycle, non-REM sleep / regulation of response to food / regulation of gastric motility / regulation of transmission of nerve impulse / gastric acid secretion / positive regulation of corticotropin secretion / positive regulation of cortisol secretion / growth hormone secretion / positive regulation of growth rate / positive regulation of eating behavior / positive regulation of small intestine smooth muscle contraction / positive regulation of appetite / adult feeding behavior / positive regulation of growth hormone secretion / protein tyrosine kinase activator activity / positive regulation of growth hormone receptor signaling pathway / positive regulation of multicellular organism growth / actin polymerization or depolymerization / positive regulation of synapse assembly / cartilage development / negative regulation of interleukin-1 beta production / positive regulation of vascular endothelial cell proliferation / regulation of postsynapse organization / postsynaptic modulation of chemical synaptic transmission / positive regulation of sprouting angiogenesis / dendrite development / negative regulation of endothelial cell proliferation / positive regulation of insulin secretion involved in cellular response to glucose stimulus / negative regulation of interleukin-6 production / negative regulation of tumor necrosis factor production / decidualization / Synthesis, secretion, and deacylation of Ghrelin / positive regulation of adipose tissue development / negative regulation of insulin secretion / hormone-mediated signaling pathway / negative regulation of angiogenesis / response to electrical stimulus / synapse assembly / Peptide ligand-binding receptors / excitatory postsynaptic potential / response to hormone / G protein-coupled receptor binding / negative regulation of inflammatory response / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / positive regulation of insulin secretion / Schaffer collateral - CA1 synapse / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / 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 / response to estrogen / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / glucose metabolic process / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / positive regulation of cold-induced thermogenesis / phospholipase C-activating G protein-coupled receptor signaling pathway / regulation of cell population proliferation / positive regulation of cytosolic calcium ion concentration Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Lama glama (llama) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
Authors | Wang Y / Zhuang Y / Xu P / Xu HE / Jiang Y | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nat Commun / Year: 2021 Title: Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor. Authors: Yue Wang / Shimeng Guo / Youwen Zhuang / Ying Yun / Peiyu Xu / Xinheng He / Jia Guo / Wanchao Yin / H Eric Xu / Xin Xie / Yi Jiang / Abstract: Ghrelin, also called "the hunger hormone", is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward, cognition, learning and memory. One unique feature ...Ghrelin, also called "the hunger hormone", is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward, cognition, learning and memory. One unique feature of ghrelin is its acylation, primarily with an octanoic acid, which is essential for its binding and activation of the ghrelin receptor, a G protein-coupled receptor. The multifaceted roles of ghrelin make ghrelin receptor a highly attractive drug target for growth retardation, obesity, and metabolic disorders. Here we present two cryo-electron microscopy structures of G-coupled ghrelin receptor bound to ghrelin and a synthetic agonist, GHRP-6. Analysis of these two structures reveals a unique binding pocket for the octanoyl group, which guides the correct positioning of the peptide to initiate the receptor activation. Together with mutational and functional data, our structures define the rules for recognition of the acylated peptide hormone and activation of ghrelin receptor, and provide structural templates to facilitate drug design targeting ghrelin receptor. | |||||||||
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_31500.map.gz | 27.1 MB | EMDB map data format | |
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Header (meta data) | emd-31500-v30.xml emd-31500.xml | 16.4 KB 16.4 KB | Display Display | EMDB header |
Images | emd_31500.png | 54.9 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31500 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31500 | HTTPS FTP |
-Validation report
Summary document | emd_31500_validation.pdf.gz | 345.4 KB | Display | EMDB validaton report |
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Full document | emd_31500_full_validation.pdf.gz | 345 KB | Display | |
Data in XML | emd_31500_validation.xml.gz | 5.7 KB | Display | |
Data in CIF | emd_31500_validation.cif.gz | 6.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31500 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31500 | HTTPS FTP |
-Related structure data
Related structure data | 7f9yMC 7f9zC 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_31500.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.071 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : ghrelin-bound ghrelin receptor in complex with Gq
Entire | Name: ghrelin-bound ghrelin receptor in complex with Gq |
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Components |
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-Supramolecule #1: ghrelin-bound ghrelin receptor in complex with Gq
Supramolecule | Name: ghrelin-bound ghrelin receptor in complex with Gq / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
-Macromolecule #1: Engineered G-alpha-q subunit
Macromolecule | Name: Engineered G-alpha-q subunit / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 41.855578 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MMGCTLSAED KAAVERSKMI EKQLQKDKQV YRRTLRLLLL GADNSGKSTI VKQMRIYHVN GYSEEECKQY KAVVYSNTIQ SIIAIIRAM GRLKIDFGDS ARADDARQLF VLAGAAEEGF MTAELAGVIK RLWKDSGVQA CFNRSREYQL NDSAAYYLND L DRIAQPNY ...String: MMGCTLSAED KAAVERSKMI EKQLQKDKQV YRRTLRLLLL GADNSGKSTI VKQMRIYHVN GYSEEECKQY KAVVYSNTIQ SIIAIIRAM GRLKIDFGDS ARADDARQLF VLAGAAEEGF MTAELAGVIK RLWKDSGVQA CFNRSREYQL NDSAAYYLND L DRIAQPNY IPTQQDVLRT RVKTSGIFET KFQVDKVNFH MFDVGAQRDE RRKWIQCFND VTAIIFVVDS SDYNRLQEAL ND FKSIWNN RWLRTISVIL FLNKQDLLAE KVLAGKSKIE DYFPEFARYT TPEDATPEPG EDPRVTRAKY FIRKEFVDIS TAS GDGRHI CYPHFTCSVD TENARRIFND CKDIILQMNL REYNLV |
-Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 40.226992 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD ...String: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD TTCALWDIET GQQTTTFTGH TGDVMSLSLA PDTRLFVSGA CDASAKLWDV REGMCRQTFT GHESDINAIC FF PNGNAFA TGSDDATCRL FDLRADQELM TYSHDNIICG ITSVSFSKSG RLLLAGYDDF NCNVWDALKA DRAGVLAGHD NRV SCLGVT DDGMAVATGS WDSFLKIWNG SSGGGGSGGG GSSGVSGWRL FKKIS |
-Macromolecule #3: Ghrelin-28
Macromolecule | Name: Ghrelin-28 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 3.252726 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: GSSFLSPEHQ RVQQRKESKK PPAKLQPR |
-Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-Macromolecule #5: NB35
Macromolecule | Name: NB35 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Lama glama (llama) |
Molecular weight | Theoretical: 15.343019 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MAQVQLQESG GGLVQPGGSL RLSCAASGFT FSNYKMNWVR QAPGKGLEWV SDISQSGASI SYTGSVKGRF TISRDNAKNT LYLQMNSLK PEDTAVYYCA RCPAPFTRDC FDVTSTTYAY RGQGTQVTVS SHHHHHHEPE A |
-Macromolecule #6: Soluble cytochrome b562
Macromolecule | Name: Soluble cytochrome b562 / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 74.282609 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MKTIIALSYI FCLVFAHHHH HHHHHHADLE DNWETLNDNL KVIEKADNAA QVKDALTKMR AAALDAQKAT PPKLEDKSPD SPEMKDFRH GFDILVGQID DALKLANEGK VKEAQAAAEQ LKTTRNAYIQ KYLMWNATPS EEPGFNLTLA DLDWDASPGN D SLGDELLQ ...String: MKTIIALSYI FCLVFAHHHH HHHHHHADLE DNWETLNDNL KVIEKADNAA QVKDALTKMR AAALDAQKAT PPKLEDKSPD SPEMKDFRH GFDILVGQID DALKLANEGK VKEAQAAAEQ LKTTRNAYIQ KYLMWNATPS EEPGFNLTLA DLDWDASPGN D SLGDELLQ LFPAPLLAGV TATCVALFVV GIAGNLLTML VVSRFRELRT TTNLYLSSMA FSDLLIFLCM PLDLVRLWQY RP WNFGDLL CKLFQFVSES CTYATVLTIT ALSVERYFAI CFPLRAKVVV TKGRVKLVIF VIWAVAFCSA GPIFVLVGVE HEN GTDPWD TNECRPTEFA VRSGLLTVMV WVSSIFFFLP VFCLTVLYSL IGRKLWRRRR GDAVVGASLR DQNHKQTVKM LAVV VFAFI LCWLPFHVGR YLFSKSFEPG SLEIAQISQY CNLVSFVLFY LSAAINPILY NIMSKKYRVA VFRLLGFEPF SQRKL STLK DESSRAWTES SINTGSAGSV FTLEDFVGDW EQTAAYNLDQ VLEQGGVSSL LQNLAVSVTP IQRIVRSGEN ALKIDI HVI IPYEGLSADQ MAQIEEVFKV VYPVDDHHFK VILPYGTLVI DGVTPNMLNY FGRPYEGIAV FDGKKITVTG TLWNGNK II DERLITPDGS MLFRVTINS |
-Macromolecule #7: OCTANOIC ACID (CAPRYLIC ACID)
Macromolecule | Name: OCTANOIC ACID (CAPRYLIC ACID) / type: ligand / ID: 7 / Number of copies: 1 / Formula: OCA |
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Molecular weight | Theoretical: 144.211 Da |
Chemical component information | ChemComp-OCA: |
-Macromolecule #8: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 8 / Number of copies: 2 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ChemComp-CLR: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 80.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 522055 |
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Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |