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- PDB-7f8v: Cryo-EM structure of the cholecystokinin receptor CCKBR in comple... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7f8v | |||||||||||||||||||||||||||||||||
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Title | Cryo-EM structure of the cholecystokinin receptor CCKBR in complex with gastrin-17 and Gi | |||||||||||||||||||||||||||||||||
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![]() | STRUCTURAL PROTEIN / G protein-coulped receptor / Cholecystokinin receptor CCKBR / Gastrin-17 | |||||||||||||||||||||||||||||||||
Function / homology | ![]() gastrin receptor activity / type B gastrin/cholecystokinin receptor binding / gland development / gastric acid secretion / cholecystokinin receptor activity / cholecystokinin signaling pathway / pH reduction / 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 / cholecystokinin receptor activity / cholecystokinin signaling pathway / pH reduction / 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 / 1-phosphatidylinositol-3-kinase regulator activity / negative regulation of adenylate cyclase activity / Gastrin-CREB signalling pathway via PKC and MAPK / positive regulation of neural precursor cell proliferation / 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 / response to nutrient / positive regulation of insulin receptor signaling pathway / positive regulation of superoxide anion generation / positive regulation of vascular associated smooth muscle cell proliferation / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / 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 / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / midbody / G alpha (i) signalling events / cell body / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / positive regulation of ERK1 and ERK2 cascade / cell surface receptor signaling pathway / positive regulation of cell migration / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / intracellular membrane-bounded organelle / GTPase activity / centrosome / positive regulation of cell population proliferation / synapse / dendrite / protein-containing complex binding / GTP binding / signal transduction Similarity search - Function | |||||||||||||||||||||||||||||||||
Biological species | ![]() | |||||||||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||||||||||||||||||||||||||
![]() | Zhang, X. / He, C. / Wang, M. / Zhou, Q. / Yang, D. / Zhu, Y. / Wu, B. / Zhao, Q. | |||||||||||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() 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
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 164.4 KB | Display | ![]() |
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PDB format | ![]() | 126.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 31493MC ![]() 7f8uC ![]() 7f8wC ![]() 7f8xC ![]() 7f8yC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 40502.863 Da / Num. of mol.: 1 / Mutation: S47N, G204A, E246A, A327S Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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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.) ![]() ![]() |
#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#4: Protein/peptide | Mass: 2098.203 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
#5: Protein | Mass: 50524.922 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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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 |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 1.75 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1338153 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 48.26 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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