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Yorodumi- PDB-7f8w: Cryo-EM structure of the cholecystokinin receptor CCKBR in comple... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7f8w | |||||||||||||||||||||||||||||||||
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Title | Cryo-EM structure of the cholecystokinin receptor CCKBR in complex with gastrin-17 and Gq | |||||||||||||||||||||||||||||||||
Components |
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Keywords | STRUCTURAL PROTEIN / G protein-coulped receptor / Cholecystokinin receptor CCKBR / Gastrin-17 | |||||||||||||||||||||||||||||||||
Function / homology | Function and homology information gastrin receptor activity / type B gastrin/cholecystokinin receptor binding / gland development / pH reduction / gastric acid secretion / cholecystokinin receptor activity / cholecystokinin signaling pathway / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / PLC beta mediated events ...gastrin receptor activity / type B gastrin/cholecystokinin receptor binding / gland development / pH reduction / gastric acid secretion / cholecystokinin receptor activity / cholecystokinin signaling pathway / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / PLC beta mediated events / phospholipase C-activating dopamine receptor signaling pathway / regulation of platelet activation / phototransduction, visible light / 1-phosphatidylinositol-3-kinase regulator activity / entrainment of circadian clock / Gastrin-CREB signalling pathway via PKC and MAPK / digestive tract development / glutamate receptor signaling pathway / regulation of canonical Wnt signaling pathway / action potential / peptide hormone binding / : / photoreceptor outer segment / Peptide ligand-binding receptors / GTPase activator activity / G protein-coupled receptor binding / negative regulation of protein kinase activity / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / 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 / 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 / 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 / blood coagulation / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / nuclear membrane / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell surface receptor signaling pathway / protein stabilization / G protein-coupled receptor signaling pathway / lysosomal membrane / intracellular membrane-bounded organelle / GTPase activity / synapse / positive regulation of cell population proliferation / protein-containing complex binding / GTP binding / Golgi apparatus / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||||||||||||||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||||||||||||||||||||||||||
Authors | Zhang, X. / He, C. / Wang, M. / Zhou, Q. / Yang, D. / Zhu, Y. / Wu, B. / Zhao, Q. | |||||||||||||||||||||||||||||||||
Funding support | China, 10items
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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 | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7f8w.cif.gz | 206.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7f8w.ent.gz | 161.4 KB | Display | PDB format |
PDBx/mmJSON format | 7f8w.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7f8w_validation.pdf.gz | 715.6 KB | Display | wwPDB validaton report |
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Full document | 7f8w_full_validation.pdf.gz | 726.1 KB | Display | |
Data in XML | 7f8w_validation.xml.gz | 34.6 KB | Display | |
Data in CIF | 7f8w_validation.cif.gz | 52.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/f8/7f8w ftp://data.pdbj.org/pub/pdb/validation_reports/f8/7f8w | HTTPS FTP |
-Related structure data
Related structure data | 31494MC 7f8uC 7f8vC 7f8xC 7f8yC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABC
#1: Protein | Mass: 41353.078 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAQ, GAQ / Production host: Baculovirus expression vector pFastBac1-HM / References: UniProt: P50148 |
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#2: Protein | Mass: 38744.371 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Baculovirus expression vector pFastBac1-HM / References: UniProt: P62873 |
#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: Baculovirus expression vector pFastBac1-HM / References: UniProt: P59768 |
-Antibody / Protein/peptide / Protein , 3 types, 3 molecules DER
#4: Antibody | Mass: 28621.141 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Baculovirus expression vector pFastBac1-HM |
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#5: Protein/peptide | Mass: 2098.203 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) |
#6: Protein | Mass: 50524.922 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CCKBR / Production host: Baculovirus expression vector pFastBac1-HM / References: UniProt: P32239 |
-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 |
-Sample preparation
Component |
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 1.75 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 354647 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 59.93 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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