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Yorodumi- EMDB-33360: Structural insights into human brain gut peptide cholecystokinin ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33360 | |||||||||
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Title | Structural insights into human brain gut peptide cholecystokinin receptors | |||||||||
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Sample |
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Function / homology | Function and homology information cholecystokinin receptor activity / cholecystokinin signaling pathway / regulation of hormone secretion / neuropeptide receptor activity / peptide hormone binding / forebrain development / cellular response to hormone stimulus / Peptide ligand-binding receptors / axonogenesis / peptide binding ...cholecystokinin receptor activity / cholecystokinin signaling pathway / regulation of hormone secretion / neuropeptide receptor activity / peptide hormone binding / forebrain development / cellular response to hormone stimulus / Peptide ligand-binding receptors / axonogenesis / peptide binding / neuron migration / 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 / 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 / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / signal transduction / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / synthetic construct (others) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
Authors | Ding Y / Zhang H / Liao Y / Chen L / Ji S | |||||||||
Funding support | China, 1 items
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Citation | Journal: Cell Discov / Year: 2022 Title: Structural insights into human brain-gut peptide cholecystokinin receptors. Authors: Yu Ding / Huibing Zhang / Yu-Ying Liao / Li-Nan Chen / Su-Yu Ji / Jiao Qin / Chunyou Mao / Dan-Dan Shen / Lin Lin / Hao Wang / Yan Zhang / Xiao-Ming Li / Abstract: The intestinal hormone and neuromodulator cholecystokinin (CCK) receptors CCK1R and CCK2R act as a signaling hub in brain-gut axis, mediating digestion, emotion, and memory regulation. CCK receptors ...The intestinal hormone and neuromodulator cholecystokinin (CCK) receptors CCK1R and CCK2R act as a signaling hub in brain-gut axis, mediating digestion, emotion, and memory regulation. CCK receptors exhibit distinct preferences for ligands in different posttranslational modification (PTM) states. CCK1R couples to G and G, whereas CCK2R primarily couples to G. Here we report the cryo-electron microscopy (cryo-EM) structures of CCK1R-G signaling complexes liganded either by sulfated cholecystokinin octapeptide (CCK-8) or a CCK1R-selective small-molecule SR146131, and CCK2R-G complexes stabilized by either sulfated CCK-8 or a CCK2R-selective ligand gastrin-17. Our structures reveal a location-conserved yet charge-distinct pocket discriminating the effects of ligand PTM states on receptor subtype preference, the unique pocket topology underlying selectivity of SR146131 and gastrin-17, the conformational changes in receptor activation, and key residues contributing to G protein subtype specificity, providing multiple structural templates for drug design targeting the brain-gut axis. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_33360.map.gz | 24.1 MB | EMDB map data format | |
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Header (meta data) | emd-33360-v30.xml emd-33360.xml | 21.2 KB 21.2 KB | Display Display | EMDB header |
Images | emd_33360.png | 23.9 KB | ||
Others | emd_33360_half_map_1.map.gz emd_33360_half_map_2.map.gz | 23.4 MB 23.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33360 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33360 | HTTPS FTP |
-Validation report
Summary document | emd_33360_validation.pdf.gz | 627.8 KB | Display | EMDB validaton report |
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Full document | emd_33360_full_validation.pdf.gz | 627.3 KB | Display | |
Data in XML | emd_33360_validation.xml.gz | 10.5 KB | Display | |
Data in CIF | emd_33360_validation.cif.gz | 12.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33360 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33360 | HTTPS FTP |
-Related structure data
Related structure data | 7xovMC 7xouC 7xowC 8ia7C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_33360.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.014 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_33360_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_33360_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : cholecystokinin receptor1
+Supramolecule #1: cholecystokinin receptor1
+Supramolecule #2: cholecystokinin receptor1
+Supramolecule #3: Gs protein
+Supramolecule #4: Nanobody35
+Macromolecule #1: Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit...
+Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #4: Nanobody 35
+Macromolecule #5: Cholecystokinin receptor type A
+Macromolecule #6: 2-[2-[[4-(4-chloranyl-2,5-dimethoxy-phenyl)-5-(2-cyclohexylethyl)...
+Macromolecule #7: water
-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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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 62.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 5.0 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 606654 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |