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Yorodumi- PDB-7f8y: Crystal structure of the cholecystokinin receptor CCKAR in comple... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7f8y | |||||||||||||||||||||||||||||||||
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Title | Crystal structure of the cholecystokinin receptor CCKAR in complex with devazepide | |||||||||||||||||||||||||||||||||
Components | fusion protein of Cholecystokinin receptor type A and Endolysin | |||||||||||||||||||||||||||||||||
Keywords | STRUCTURAL PROTEIN / G protein-coulped receptor / Cholecystokinin receptor CCKAR / devazepide | |||||||||||||||||||||||||||||||||
Function / homology | Function and homology information cholecystokinin receptor activity / cholecystokinin signaling pathway / regulation of hormone secretion / peptide hormone binding / cellular response to hormone stimulus / viral release from host cell by cytolysis / forebrain development / peptidoglycan catabolic process / Peptide ligand-binding receptors / axonogenesis ...cholecystokinin receptor activity / cholecystokinin signaling pathway / regulation of hormone secretion / peptide hormone binding / cellular response to hormone stimulus / viral release from host cell by cytolysis / forebrain development / peptidoglycan catabolic process / Peptide ligand-binding receptors / axonogenesis / peptide binding / neuron migration / cell wall macromolecule catabolic process / lysozyme / lysozyme activity / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / host cell cytoplasm / defense response to bacterium / G protein-coupled receptor signaling pathway / nucleoplasm / membrane / plasma membrane / cytosol Similarity search - Function | |||||||||||||||||||||||||||||||||
Biological species | Homo sapiens (human) Enterobacteria phage T4 (virus) | |||||||||||||||||||||||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5 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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7f8y.cif.gz | 214.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7f8y.ent.gz | 149.3 KB | Display | PDB format |
PDBx/mmJSON format | 7f8y.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7f8y_validation.pdf.gz | 725.9 KB | Display | wwPDB validaton report |
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Full document | 7f8y_full_validation.pdf.gz | 734.2 KB | Display | |
Data in XML | 7f8y_validation.xml.gz | 17.4 KB | Display | |
Data in CIF | 7f8y_validation.cif.gz | 23.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/f8/7f8y ftp://data.pdbj.org/pub/pdb/validation_reports/f8/7f8y | HTTPS FTP |
-Related structure data
Related structure data | 7f8uC 7f8vC 7f8wC 7f8xC 5zbqS S: Starting model for refinement 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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Unit cell |
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-Components
#1: Protein | Mass: 60450.367 Da / Num. of mol.: 1 / Mutation: D87N,F130W,R1251G,G1293T,C1336A,I385R Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human), (gene. exp.) Enterobacteria phage T4 (virus) Gene: CCKAR, CCKRA / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P32238, UniProt: P00720, lysozyme |
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#2: Chemical | ChemComp-1OZ / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.76 Å3/Da / Density % sol: 55.43 % |
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Crystal grow | Temperature: 293 K / Method: lipidic cubic phase Details: 0.1 M HEPES, pH 7.5, 25% (v/v) PEG400 and 350 mM ammonium acetate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SPring-8 / Beamline: BL41XU / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 25, 2016 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.5→50 Å / Num. obs: 39065 / % possible obs: 99.3 % / Redundancy: 4.8 % / Biso Wilson estimate: 68.07 Å2 / CC1/2: 0.986 / Net I/σ(I): 5 |
Reflection shell | Resolution: 2.5→2.56 Å / Mean I/σ(I) obs: 1 / Num. unique obs: 2194 / CC1/2: 0.679 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5ZBQ Resolution: 2.5→29.77 Å / SU ML: 0.4634 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 33.5385 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 80.06 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.5→29.77 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: 8.92821277326 Å / Origin y: 17.7892190846 Å / Origin z: 24.340940478 Å
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Refinement TLS group | Selection details: all |