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Yorodumi- EMDB-31493: Cryo-EM structure of the cholecystokinin receptor CCKBR in comple... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31493 | |||||||||||||||||||||||||||||||||
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Title | Cryo-EM structure of the cholecystokinin receptor CCKBR in complex with gastrin-17 and Gi | |||||||||||||||||||||||||||||||||
Map data | CCKBR-Gi complex | |||||||||||||||||||||||||||||||||
Sample |
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Function / homology | Function and homology information gastrin receptor activity / type B gastrin/cholecystokinin receptor binding / gland development / gastric acid secretion / pH reduction / cholecystokinin receptor activity / cholecystokinin signaling pathway / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / G protein-coupled adenosine receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis ...gastrin receptor activity / type B gastrin/cholecystokinin receptor binding / gland development / gastric acid secretion / pH reduction / cholecystokinin receptor activity / cholecystokinin signaling pathway / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / G protein-coupled adenosine receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis / positive regulation of urine volume / negative regulation of adenylate cyclase activity / 1-phosphatidylinositol-3-kinase regulator activity / positive regulation of neural precursor cell proliferation / Gastrin-CREB signalling pathway via PKC and MAPK / digestive tract development / gamma-aminobutyric acid signaling pathway / negative regulation of synaptic transmission / neuronal dense core vesicle / peptide hormone binding / regulation of calcium ion transport / negative regulation of apoptotic signaling pathway / Adenylate cyclase inhibitory pathway / positive regulation of insulin receptor signaling pathway / positive regulation of vascular associated smooth muscle cell proliferation / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / response to nutrient / positive regulation of superoxide anion generation / Regulation of insulin secretion / G protein-coupled receptor binding / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / 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 / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / sensory perception of taste / GPER1 signaling / G-protein beta-subunit binding / heterotrimeric G-protein complex / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / G alpha (12/13) signalling events / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / GTPase binding / cell body / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / midbody / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / positive regulation of ERK1 and ERK2 cascade / cell surface receptor signaling pathway / positive regulation of cell migration / cell cycle / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / intracellular membrane-bounded organelle / GTPase activity / centrosome / dendrite / synapse / positive regulation of cell population proliferation / protein-containing complex binding / GTP binding Similarity search - Function | |||||||||||||||||||||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||||||||||||||||||||||||||
Authors | Zhang X / He C / Wang M / Zhou Q / Yang D / Zhu Y / Wu B / Zhao Q | |||||||||||||||||||||||||||||||||
Funding support | China, 10 items
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Citation | Journal: Nat Chem Biol / Year: 2021 Title: Structures of the human cholecystokinin receptors bound to agonists and antagonists. Authors: Xuefeng Zhang / Chenglin He / Mu Wang / Qingtong Zhou / Dehua Yang / Ya Zhu / Wenbo Feng / Hui Zhang / Antao Dai / Xiaojing Chu / Jia Wang / Zhenlin Yang / Yi Jiang / Ulrich Sensfuss / ...Authors: Xuefeng Zhang / Chenglin He / Mu Wang / Qingtong Zhou / Dehua Yang / Ya Zhu / Wenbo Feng / Hui Zhang / Antao Dai / Xiaojing Chu / Jia Wang / Zhenlin Yang / Yi Jiang / Ulrich Sensfuss / Qiuxiang Tan / Shuo Han / Steffen Reedtz-Runge / H Eric Xu / Suwen Zhao / Ming-Wei Wang / Beili Wu / Qiang Zhao / Abstract: Cholecystokinin receptors, CCKR and CCKR, are important neurointestinal peptide hormone receptors and play a vital role in food intake and appetite regulation. Here, we report three crystal ...Cholecystokinin receptors, CCKR and CCKR, are important neurointestinal peptide hormone receptors and play a vital role in food intake and appetite regulation. Here, we report three crystal structures of the human CCKR in complex with different ligands, including one peptide agonist and two small-molecule antagonists, as well as two cryo-electron microscopy structures of CCKR-gastrin in complex with G and G, respectively. These structures reveal the recognition pattern of different ligand types and the molecular basis of peptide selectivity in the cholecystokinin receptor family. By comparing receptor structures in different conformational states, a stepwise activation process of cholecystokinin receptors is proposed. Combined with pharmacological data, our results provide atomic details for differential ligand recognition and receptor activation mechanisms. These insights will facilitate the discovery of potential therapeutics targeting cholecystokinin 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_31493.map.gz | 6.5 MB | EMDB map data format | |
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Header (meta data) | emd-31493-v30.xml emd-31493.xml | 18.9 KB 18.9 KB | Display Display | EMDB header |
Images | emd_31493.png | 95.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31493 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31493 | HTTPS FTP |
-Related structure data
Related structure data | 7f8vMC 7f8uC 7f8wC 7f8xC 7f8yC C: citing same article (ref.) M: atomic model generated by this map |
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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_31493.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | CCKBR-Gi complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.045 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 : Cholecystokinin recetor CCKBR in complex with gastrin-17 and Gi
Entire | Name: Cholecystokinin recetor CCKBR in complex with gastrin-17 and Gi |
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Components |
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-Supramolecule #1: Cholecystokinin recetor CCKBR in complex with gastrin-17 and Gi
Supramolecule | Name: Cholecystokinin recetor CCKBR in complex with gastrin-17 and Gi type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Baculovirus expression vector pFastBac1-HM |
-Supramolecule #2: Guanine nucleotide-binding protein G(i) subunit
Supramolecule | Name: Guanine nucleotide-binding protein G(i) subunit / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#3, #5 |
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-Supramolecule #3: Gastrin-17
Supramolecule | Name: Gastrin-17 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #4 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #4: cholecystokinin type B receptor
Supramolecule | Name: cholecystokinin type B receptor / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #5 |
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-Macromolecule #1: Guanine nucleotide-binding protein G(i) subunit alpha-2
Macromolecule | Name: Guanine nucleotide-binding protein G(i) subunit alpha-2 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: 40.502863 KDa |
Recombinant expression | Organism: Baculovirus expression vector pFastBac1-HM |
Sequence | String: MGCTVSAEDK AAAERSKMID KNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEDG YSEEECRQYR AVVYSNTIQS IMAIVKAMG NLQIDFADPS RADDARQLFA LSCTAEEQGV LPDDLSGVIR RLWADHGVQA CFGRSREYQL NDSAAYYLND L ERIAQSDY ...String: MGCTVSAEDK AAAERSKMID KNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEDG YSEEECRQYR AVVYSNTIQS IMAIVKAMG NLQIDFADPS RADDARQLFA LSCTAEEQGV LPDDLSGVIR RLWADHGVQA CFGRSREYQL NDSAAYYLND L ERIAQSDY IPTQQDVLRT RVKTTGIVET HFTFKDLHFK MFDVGAQRSE RKKWIHCFEG VTAIIFCVAL SAYDLVLAED EE MNRMHAS MKLFDSICNN KWFTDTSIIL FLNKKDLFEE KITHSPLTIC FPEYTGANKY DEAASYIQSK FEDLNKRKDT KEI YTHFTC STDTKNVQFV FDAVTDVIIK NNLKDCGLF |
-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: 38.744371 KDa |
Recombinant expression | Organism: Baculovirus expression vector pFastBac1-HM |
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 #3: 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: 3 / 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: Baculovirus expression vector pFastBac1-HM |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-Macromolecule #4: Gastrin-17
Macromolecule | Name: Gastrin-17 / 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: 2.098203 KDa |
Sequence | String: (PCA)GPWLEEEEE AYGWMD(NFA) |
-Macromolecule #5: Gastrin/cholecystokinin type B receptor
Macromolecule | Name: Gastrin/cholecystokinin type B receptor / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 50.524922 KDa |
Recombinant expression | Organism: Baculovirus expression vector pFastBac1-HM |
Sequence | String: DYKDDDDGAP ELLKLNRSVQ GTGPGPGASL CRPGAPLLNS SSVGNLSCEP PRIRGAGTRE LELAIRITLY AVIFLMSVGG NMLIIVVLG LSRRLRTVTN AFLLSLAVSD LLLAVACMPF TLLPNLMGTF IFGTVICKAV SYLMGVSVSV STLSLVAIAL E RYSAICRP ...String: DYKDDDDGAP ELLKLNRSVQ GTGPGPGASL CRPGAPLLNS SSVGNLSCEP PRIRGAGTRE LELAIRITLY AVIFLMSVGG NMLIIVVLG LSRRLRTVTN AFLLSLAVSD LLLAVACMPF TLLPNLMGTF IFGTVICKAV SYLMGVSVSV STLSLVAIAL E RYSAICRP LQARVWQTRS HAARVIVATW LLSGLLMVPY PVYTVVQPVG PRVLQCVHRW PSARVRQTWS VLLLLLLFFI PG VVMAVAY GLISRELYLG LRFDGDSDSD SQSRVRNQGG LPGAVHQNGR CRPETGAVGE DSDGCYVQLP RSRPALELTA LTA PGPGSG SRPTQAKLLA KKRVVRMLLV IVVLFFLCWL PVYSANTWRA FDGPGAHRAL SGAPISFIHL LSYASACVNP LVYC FMHRR FRQACLETCA RCCPRPPRAR PREFLEVLFQ GPWSHPQFEK GGGSGGGSGG SAWSHPQFEK |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 1.75 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
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Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 1338153 |