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Yorodumi- EMDB-30860: Structural basis of ligand selectivity conferred by the human glu... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30860 | |||||||||||||||
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Title | Structural basis of ligand selectivity conferred by the human glucose-dependent insulinotropic polypeptide receptor | |||||||||||||||
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Function / homology | Function and homology information gastric inhibitory polypeptide receptor binding / digestive system development / gastric inhibitory peptide signaling pathway / glucagon receptor binding / regulation of fatty acid biosynthetic process / endocrine pancreas development / positive regulation of cAMP-mediated signaling / Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) / sensory perception of chemical stimulus / response to selenium ion ...gastric inhibitory polypeptide receptor binding / digestive system development / gastric inhibitory peptide signaling pathway / glucagon receptor binding / regulation of fatty acid biosynthetic process / endocrine pancreas development / positive regulation of cAMP-mediated signaling / Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) / sensory perception of chemical stimulus / response to selenium ion / 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 / response to acidic pH / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / positive regulation of glucose transmembrane transport / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / triglyceride homeostasis / 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 / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / alkylglycerophosphoethanolamine phosphodiesterase activity / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / exploration behavior / G alpha (q) signalling events / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / response to lipid / response to starvation / regulation of insulin secretion / mu-type opioid receptor binding / photoreceptor outer segment / corticotropin-releasing hormone receptor 1 binding / response to axon injury / D1 dopamine receptor binding / response to amino acid / response to glucose / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / sensory perception of pain / cardiac muscle cell apoptotic process / adenylate cyclase activator activity / photoreceptor inner segment / adult locomotory behavior / female pregnancy / long-term synaptic potentiation / 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 / positive regulation of insulin secretion / response to organic cyclic compound / hormone activity / memory / response to peptide hormone / Glucagon-type ligand receptors / cellular response to catecholamine stimulus / sensory perception of taste / 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 / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) / Bos taurus (cattle) / Rattus norvegicus (Norway rat) / synthetic construct (others) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.98 Å | |||||||||||||||
Authors | Zhao FH / Zhang C / Zhou QT / Hang KN / Zou XY / Chen Y / Wu F / Rao QD / Dai AT / Yin WC ...Zhao FH / Zhang C / Zhou QT / Hang KN / Zou XY / Chen Y / Wu F / Rao QD / Dai AT / Yin WC / Shen DD / Zhang Y / Xia T / Stevens RC / Xu HE / Yang DH / Zhao LH / Wang MW | |||||||||||||||
Funding support | China, 4 items
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Citation | Journal: Elife / Year: 2021 Title: Structural insights into hormone recognition by the human glucose-dependent insulinotropic polypeptide receptor. Authors: Fenghui Zhao / Chao Zhang / Qingtong Zhou / Kaini Hang / Xinyu Zou / Yan Chen / Fan Wu / Qidi Rao / Antao Dai / Wanchao Yin / Dan-Dan Shen / Yan Zhang / Tian Xia / Raymond C Stevens / H Eric ...Authors: Fenghui Zhao / Chao Zhang / Qingtong Zhou / Kaini Hang / Xinyu Zou / Yan Chen / Fan Wu / Qidi Rao / Antao Dai / Wanchao Yin / Dan-Dan Shen / Yan Zhang / Tian Xia / Raymond C Stevens / H Eric Xu / Dehua Yang / Lihua Zhao / Ming-Wei Wang / Abstract: Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that exerts crucial metabolic functions by binding and activating its cognate receptor, GIPR. As an important therapeutic ...Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that exerts crucial metabolic functions by binding and activating its cognate receptor, GIPR. As an important therapeutic target, GIPR has been subjected to intensive structural studies without success. Here, we report the cryo-EM structure of the human GIPR in complex with GIP and a G heterotrimer at a global resolution of 2.9 Å. GIP adopts a single straight helix with its N terminus dipped into the receptor transmembrane domain (TMD), while the C terminus is closely associated with the extracellular domain and extracellular loop 1. GIPR employs conserved residues in the lower half of the TMD pocket to recognize the common segments shared by GIP homologous peptides, while uses non-conserved residues in the upper half of the TMD pocket to interact with residues specific for GIP. These results provide a structural framework of hormone recognition and GIPR activation. | |||||||||||||||
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_30860.map.gz | 59.3 MB | EMDB map data format | |
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Header (meta data) | emd-30860-v30.xml emd-30860.xml | 17.6 KB 17.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_30860_fsc.xml | 9.1 KB | Display | FSC data file |
Images | emd_30860.png | 12.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30860 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30860 | HTTPS FTP |
-Validation report
Summary document | emd_30860_validation.pdf.gz | 415.1 KB | Display | EMDB validaton report |
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Full document | emd_30860_full_validation.pdf.gz | 414.7 KB | Display | |
Data in XML | emd_30860_validation.xml.gz | 11.1 KB | Display | |
Data in CIF | emd_30860_validation.cif.gz | 14.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30860 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30860 | HTTPS FTP |
-Related structure data
Related structure data | 7dtyMC 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_30860.map.gz / Format: CCP4 / Size: 64 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 : Cryo-EM structure of the human glucose-dependent insulinotropic p...
Entire | Name: Cryo-EM structure of the human glucose-dependent insulinotropic polypeptide receptor in complex with GIP and G protein |
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Components |
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-Supramolecule #1: Cryo-EM structure of the human glucose-dependent insulinotropic p...
Supramolecule | Name: Cryo-EM structure of the human glucose-dependent insulinotropic polypeptide receptor in complex with GIP and G protein 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: human glucose-dependent insulinotropic polypeptide receptor
Macromolecule | Name: human glucose-dependent insulinotropic polypeptide receptor type: protein_or_peptide / ID: 1 / Details: mutations:1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 64.950695 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: RAETGSKGQT AGELYQRWER YRRECQETLA AAEPPSGLAC NGSFDMYVCW DYAAPNATAR ASCPWYLPWH HHVAAGFVLR QCGSDGQWG LWRDHTQCEN PEKNEAFLDQ RLILERLQVM YTVGYSLSLA TLLLALLILS LFRRLHCTRN YIHINLFTSF M LRAAAILS ...String: RAETGSKGQT AGELYQRWER YRRECQETLA AAEPPSGLAC NGSFDMYVCW DYAAPNATAR ASCPWYLPWH HHVAAGFVLR QCGSDGQWG LWRDHTQCEN PEKNEAFLDQ RLILERLQVM YTVGYSLSLA TLLLALLILS LFRRLHCTRN YIHINLFTSF M LRAAAILS RDRLLPRPGP YLGDQALALW NQALAACRTA QIVTQYCVGA NYTWLLVEGV YLHSLLVLVG GSEEGHFRYY LL LGWGAPA LFVIPWVIVR YLYENTQCWE RNEVKAIWWI IRTPILMTIL INFLIFIRIL GILLSKLRTR QMRCRDYRLR LAR STLFLV PLLGVHEVVF APVTEEQARG ALRFAKLGFE IFLSSFQGFL VSVLYCFINK EVQSEIRRGW HHCRLRRSLG EEQR GSSGG GGSGGGGSSG VFTLEDFVGD WEQTAAYNLD QVLEQGGVSS LLQNLAVSVT PIQRIVRSGE NALKIDIHVI IPYEG LSAD QMAQIEEVFK VVYPVDDHHF KVILPYGTLV IDGVTPNMLN YFGRPYEGIA VFDGKKITVT GTLWNGNKII DERLIT PDG SMLFRVTINS |
-Macromolecule #2: Gastric inhibitory polypeptide
Macromolecule | Name: Gastric inhibitory polypeptide / 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: 4.990586 KDa |
Sequence | String: YAEGTFISDY SIAMDKIHQQ DFVNWLLAQK GKKNDWKHNI TQ |
-Macromolecule #3: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
Macromolecule | Name: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Bos taurus (cattle) |
Molecular weight | Theoretical: 45.727441 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKNTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKA TKVQDIKNNL KEAIETIVAA MSNLVPPVEL ANPENQFRVD YILSVMNVPD FDFPPEFYEH AKALWEDEGV R ACYERSNE ...String: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKNTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKA TKVQDIKNNL KEAIETIVAA MSNLVPPVEL ANPENQFRVD YILSVMNVPD FDFPPEFYEH AKALWEDEGV R ACYERSNE YQLIDCAQYF LDKIDVIKQD DYVPSDQDLL RCRVLTSGIF ETKFQVDKVN FHMFDVGAQR DERRKWIQCF ND VTAIIFV VASSSYNMVI REDNQTNRLQ AALKLFDSIW NNKWLRDTSV ILFLNKQDLL AEKVLAGKSK IEDYFPEFAR YTT PEDATP EPGEDPRVTR AKYFIRDEFL RISTASGDGR HYCYPHFTCA VDTENIRRVF NDCRDIIQRM HLRQYELL |
-Macromolecule #4: 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: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
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 #5: 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: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Bos taurus (cattle) |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-Macromolecule #6: Nanobody-35
Macromolecule | Name: Nanobody-35 / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: synthetic construct (others) |
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 #7: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 7 / Number of copies: 6 / 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: OTHER |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |