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Yorodumi- EMDB-23750: Human Cholecystokinin 1 receptor (CCK1R) Gq chimera (mGsqi) complex -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23750 | ||||||||||||
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Title | Human Cholecystokinin 1 receptor (CCK1R) Gq chimera (mGsqi) complex | ||||||||||||
Map data | consensus map | ||||||||||||
Sample |
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Function / homology | Function and homology information cholecystokinin receptor activity / cholecystokinin signaling pathway / regulation of hormone secretion / neuropeptide hormone activity / G-protein activation / Activation of the phototransduction cascade / : / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste ...cholecystokinin receptor activity / cholecystokinin signaling pathway / regulation of hormone secretion / neuropeptide hormone activity / G-protein activation / Activation of the phototransduction cascade / : / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Ca2+ pathway / Activation of G protein gated Potassium channels / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / G alpha (i) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / alkylglycerophosphoethanolamine phosphodiesterase activity / peptide hormone receptor binding / photoreceptor outer segment membrane / eating behavior / spectrin binding / PKA activation in glucagon signalling / peptide hormone binding / hair follicle placode formation / intracellular transport / photoreceptor outer segment / Adenylate cyclase inhibitory pathway / D1 dopamine receptor binding / developmental growth / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / Hedgehog 'off' state / positive regulation of cAMP-mediated signaling / adenylate cyclase-activating adrenergic receptor signaling pathway / regulation of mitotic spindle organization / forebrain development / cellular response to forskolin / cellular response to hormone stimulus / cardiac muscle cell apoptotic process / digestion / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / activation of adenylate cyclase activity / photoreceptor inner segment / adenylate cyclase activator activity / Peptide ligand-binding receptors / axonogenesis / trans-Golgi network membrane / Regulation of insulin secretion / G protein-coupled receptor binding / peptide binding / neuron migration / G-protein beta/gamma-subunit complex binding / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / bone development / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / hormone activity / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / response to peptide hormone / Adrenaline,noradrenaline inhibits insulin secretion / platelet aggregation / Glucagon-type ligand receptors / cognition / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of GTPase activity / 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 / GDP binding / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events Similarity search - Function | ||||||||||||
Biological species | Rattus norvegicus (Norway rat) / Homo sapiens (human) / Mus musculus (house mouse) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.44 Å | ||||||||||||
Authors | Mobbs JI / Belousoff MJ / Danev R / Thal DM / Sexton PM | ||||||||||||
Funding support | Australia, Japan, 3 items
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Citation | Journal: PLoS Biol / Year: 2021 Title: Structures of the human cholecystokinin 1 (CCK1) receptor bound to Gs and Gq mimetic proteins provide insight into mechanisms of G protein selectivity. Authors: Jesse I Mobbs / Matthew J Belousoff / Kaleeckal G Harikumar / Sarah J Piper / Xiaomeng Xu / Sebastian G B Furness / Hari Venugopal / Arthur Christopoulos / Radostin Danev / Denise Wootten / ...Authors: Jesse I Mobbs / Matthew J Belousoff / Kaleeckal G Harikumar / Sarah J Piper / Xiaomeng Xu / Sebastian G B Furness / Hari Venugopal / Arthur Christopoulos / Radostin Danev / Denise Wootten / David M Thal / Laurence J Miller / Patrick M Sexton / Abstract: G protein-coupled receptors (GPCRs) are critical regulators of cellular function acting via heterotrimeric G proteins as their primary transducers with individual GPCRs capable of pleiotropic ...G protein-coupled receptors (GPCRs) are critical regulators of cellular function acting via heterotrimeric G proteins as their primary transducers with individual GPCRs capable of pleiotropic coupling to multiple G proteins. Structural features governing G protein selectivity and promiscuity are currently unclear. Here, we used cryo-electron microscopy (cryo-EM) to determine structures of the cholecystokinin (CCK) type 1 receptor (CCK1R) bound to the CCK peptide agonist, CCK-8 and 2 distinct transducer proteins, its primary transducer Gq, and the more weakly coupled Gs. As seen with other Gq/11-GPCR complexes, the Gq-α5 helix (αH5) bound to a relatively narrow pocket in the CCK1R core. Surprisingly, the backbone of the CCK1R and volume of the G protein binding pocket were essentially equivalent when Gs was bound, with the Gs αH5 displaying a conformation that arises from "unwinding" of the far carboxyl-terminal residues, compared to canonically Gs coupled receptors. Thus, integrated changes in the conformations of both the receptor and G protein are likely to play critical roles in the promiscuous coupling of individual GPCRs. #1: Journal: Biorxiv / Year: 2021 Title: Structures of the human cholecystokinin 1 (CCK1) receptor bound to Gs and Gq mimetic proteins: insight into mechanisms of G protein selectivity Authors: Mobbs J / Belousoff MJ / Harikumar KG / Piper SJ / Xu X / Furness SGB / Venugopal H / Christopoulos A / Danev R / Wootten D / Thal DM / Miller LJ / Sexton PM | ||||||||||||
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_23750.map.gz | 62 MB | EMDB map data format | |
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Header (meta data) | emd-23750-v30.xml emd-23750.xml | 36.2 KB 36.2 KB | Display Display | EMDB header |
Images | emd_23750.png | 122.8 KB | ||
Masks | emd_23750_msk_1.map emd_23750_msk_2.map emd_23750_msk_3.map | 125 MB 125 MB 125 MB | Mask map | |
Others | emd_23750_additional_1.map.gz emd_23750_additional_2.map.gz emd_23750_additional_3.map.gz emd_23750_additional_4.map.gz emd_23750_additional_5.map.gz emd_23750_additional_6.map.gz emd_23750_half_map_1.map.gz emd_23750_half_map_2.map.gz | 116 MB 62 MB 116.1 MB 116.1 MB 62.4 MB 116 MB 116 MB 115.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23750 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23750 | HTTPS FTP |
-Related structure data
Related structure data | 7mbyMC 7mbxC M: atomic model generated by this map C: citing same article (ref.) |
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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_23750.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | consensus map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.65 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
+Mask #1
+Mask #2
+Mask #3
+Additional map: receptor focused half map A
+Additional map: Receptor focused
+Additional map: G protein focused
+Additional map: G protein focused map
+Additional map: G protein focused map
+Additional map: receptor focused half map B
+Half map: consensus half map 2
+Half map: consensus half map 1
-Sample components
+Entire : CCK1R/CCK-8/mGsqi complex
+Supramolecule #1: CCK1R/CCK-8/mGsqi complex
+Supramolecule #2: G protein subunit beta-1
+Supramolecule #3: G(sqi)-alpha/G protein subunit gamma-2
+Supramolecule #4: CCK1R
+Supramolecule #5: CCK-8
+Supramolecule #6: scFv16
+Macromolecule #1: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #3: Cholecystokinin-8
+Macromolecule #4: Cholecystokinin receptor type A
+Macromolecule #5: Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine n...
+Macromolecule #6: CHOLESTEROL HEMISUCCINATE
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 63.9 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: 2.44 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 444000 |