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Yorodumi- EMDB-8653: Cryo-EM structure of the activated Glucagon-like peptide-1 recept... -
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-Basic information
Entry | Database: EMDB / ID: EMD-8653 | |||||||||
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Title | Cryo-EM structure of the activated Glucagon-like peptide-1 receptor in complex with G protein | |||||||||
Map data | Structure of the activated Glucagon-like peptide-1 receptor in complex with G protein | |||||||||
Sample |
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Function / homology | Function and homology information glucagon receptor binding / glucagon receptor activity / 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 ...glucagon receptor binding / glucagon receptor activity / 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 / Ca2+ pathway / negative regulation of execution phase of apoptosis / Activation of G protein gated Potassium channels / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / feeding behavior / G alpha (q) signalling events / 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 / Adrenaline,noradrenaline inhibits insulin secretion / 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 / alkylglycerophosphoethanolamine phosphodiesterase activity / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / 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 / Extra-nuclear estrogen signaling / G alpha (z) signalling events / G alpha (s) signalling events / 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 / cellular response to glucagon stimulus / positive regulation of calcium ion import / positive regulation of insulin secretion involved in cellular response to glucose stimulus / PKA activation in glucagon signalling / regulation of insulin secretion / hair follicle placode formation / intracellular transport / photoreceptor outer segment / D1 dopamine receptor binding / developmental growth / Synthesis, secretion, and deacylation of Ghrelin / Hedgehog 'off' state / positive regulation of cAMP-mediated signaling / adenylate cyclase-activating adrenergic receptor signaling pathway / protein kinase A signaling / positive regulation of gluconeogenesis / cardiac muscle cell apoptotic process / activation of adenylate cyclase activity / photoreceptor inner segment / adenylate cyclase activator activity / response to activity / trans-Golgi network membrane / positive regulation of peptidyl-threonine phosphorylation / gluconeogenesis / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / bone development / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / adenylate cyclase-activating G protein-coupled receptor signaling pathway / hormone activity / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / platelet aggregation / cognition / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of GTPase activity / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / sensory perception of taste / GPER1 signaling / G-protein beta-subunit binding Similarity search - Function | |||||||||
Biological species | Oryctolagus cuniculus (rabbit) / Homo sapiens (human) / Rattus norvegicus (Norway rat) / Bos taurus (cattle) / Lama glama (llama) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.1 Å | |||||||||
Authors | Zhang Y / Sun B / Feng D / Hu H / Chu M / Qu Q / Tarrasch JT / Li S / Kobilka TS / Kobilka BK / Skiniotis G | |||||||||
Citation | Journal: Nature / Year: 2017 Title: Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein. Authors: Yan Zhang / Bingfa Sun / Dan Feng / Hongli Hu / Matthew Chu / Qianhui Qu / Jeffrey T Tarrasch / Shane Li / Tong Sun Kobilka / Brian K Kobilka / Georgios Skiniotis / Abstract: Glucagon-like peptide 1 (GLP-1) is a hormone with essential roles in regulating insulin secretion, carbohydrate metabolism and appetite. GLP-1 effects are mediated through binding to the GLP-1 ...Glucagon-like peptide 1 (GLP-1) is a hormone with essential roles in regulating insulin secretion, carbohydrate metabolism and appetite. GLP-1 effects are mediated through binding to the GLP-1 receptor (GLP-1R), a class B G-protein-coupled receptor (GPCR) that signals primarily through the stimulatory G protein G. Class B GPCRs are important therapeutic targets; however, our understanding of their mechanism of action is limited by the lack of structural information on activated and full-length receptors. Here we report the cryo-electron microscopy structure of the peptide-activated GLP-1R-G complex at near atomic resolution. The peptide is clasped between the N-terminal domain and the transmembrane core of the receptor, and further stabilized by extracellular loops. Conformational changes in the transmembrane domain result in a sharp kink in the middle of transmembrane helix 6, which pivots its intracellular half outward to accommodate the α5-helix of the Ras-like domain of G. These results provide a structural framework for understanding class B GPCR activation through hormone binding. | |||||||||
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_8653.map.gz | 4.4 MB | EMDB map data format | |
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Header (meta data) | emd-8653-v30.xml emd-8653.xml | 17.6 KB 17.6 KB | Display Display | EMDB header |
Images | emd_8653.png | 36.9 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-8653 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8653 | HTTPS FTP |
-Related structure data
Related structure data | 5vaiMC 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_8653.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Structure of the activated Glucagon-like peptide-1 receptor in complex with G protein | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1 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 : the activated glucagon-like peptide-1 receptor in complex with th...
Entire | Name: the activated glucagon-like peptide-1 receptor in complex with the heterotrimeric Gs protein |
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Components |
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-Supramolecule #1: the activated glucagon-like peptide-1 receptor in complex with th...
Supramolecule | Name: the activated glucagon-like peptide-1 receptor in complex with the heterotrimeric Gs protein type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Oryctolagus cuniculus (rabbit) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Molecular weight | Theoretical: 150 KDa |
-Macromolecule #1: Uncharacterized protein
Macromolecule | Name: Uncharacterized protein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Oryctolagus cuniculus (rabbit) |
Molecular weight | Theoretical: 52.581793 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MKTIIALSYI FCLVFADYKD DDDAAAGQPG NGSAFLLAPN RSHAPGGGGS LEVLFQGPGG GSRPQGATVS LSETVQKWRE YRRQCQHFL TEAPPLATGL FCNRTFDDYA CWPDGAPGSF VNVSCPWYLP WASNVLQGHV YRFCTAEGHW LPKDNSSLPW R DLSECEES ...String: MKTIIALSYI FCLVFADYKD DDDAAAGQPG NGSAFLLAPN RSHAPGGGGS LEVLFQGPGG GSRPQGATVS LSETVQKWRE YRRQCQHFL TEAPPLATGL FCNRTFDDYA CWPDGAPGSF VNVSCPWYLP WASNVLQGHV YRFCTAEGHW LPKDNSSLPW R DLSECEES RRGEKSSPEE RLLSLYIIYT VGYALSFSAL VIASAILLGF RHLHCTRNYI HLNLFASFIL RALSVFIKDA AL KWMYSTA AQQHQWDGLL SYQDSLGCRL VFLLMQYCVA ANYYWLLVEG AYLYTLLAFA VFSEQRIFKL YLSIGWGVPL LFV IPWGIV KYLYEDEGCW TRNSNMNYWL IIRLPILFAI GVNFLIFIRV ICIVVSKLKA NLMCKTDIKC RLAKSTLTLI PLLG THEVI FAFVMDEHAR GTLRFVKLFT ELSFTSFQGL MVAILYCFVN NEVQMEFRKS WERWRL |
-Macromolecule #2: Glucagon-like peptide 1
Macromolecule | Name: Glucagon-like peptide 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: 3.359699 KDa |
Sequence | String: HAEGTFTSDV SSYLEGQAAK EFIAWLVKGR G |
-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: Homo sapiens (human) |
Molecular weight | Theoretical: 44.370168 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKSTIVKQM RILHVNGFNG DSEKATKVQD IKNNLKEAI ETIVAAMSNL VPPVELANPE NQFRVDYILS VMNVPDFDFP PEFYEHAKAL WEDEGVRACY ERSNEYQLID C AQYFLDKI ...String: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKSTIVKQM RILHVNGFNG DSEKATKVQD IKNNLKEAI ETIVAAMSNL VPPVELANPE NQFRVDYILS VMNVPDFDFP PEFYEHAKAL WEDEGVRACY ERSNEYQLID C AQYFLDKI DVIKQDDYVP SDQDLLRCRV LTSGIFETKF QVDKVNFHMF DVGGQRDERR KWIQCFNDVT AIIFVVASSS YN MVIREDN QTNRLQEALN LFKSIWNNRW LRTISVILFL NKQDLLAEKV LAGKSKIEDY FPEFARYTTP EDATPEPGED PRV TRAKYF IRDEFLRIST ASGDGRHYCY PHFTCAVDTE NIRRVFNDCR DIIQRMHLRQ YELL |
-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: 38.744371 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI ...String: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI VTSSGDTTCA LWDIETGQQT TTFTGHTGDV MSLSLAPDTR LFVSGACDAS AKLWDVREGM CRQTFTGHES DI NAICFFP NGNAFATGSD DATCRLFDLR ADQELMTYSH DNIICGITSV SFSKSGRLLL AGYDDFNCNV WDALKADRAG VLA GHDNRV SCLGVTDDGM AVATGSWDSF LKIWN |
-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: 7.56375 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFC |
-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: Lama glama (llama) |
Molecular weight | Theoretical: 15.140742 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSSH HHHHHEPEA |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated magnification: 50000 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 29000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 90.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER / Details: initial model was generated using VIPER |
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Initial angle assignment | Type: PROJECTION MATCHING |
Final 3D classification | Software - Name: RELION (ver. 1.4) |
Final angle assignment | Type: PROJECTION MATCHING |
Final reconstruction | Number classes used: 1 / Applied symmetry - Point group: C1 (asymmetric) / Algorithm: BACK PROJECTION / Resolution.type: BY AUTHOR / Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 1.4) / Number images used: 139299 |