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Open data
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Basic information
Entry | Database: PDB / ID: 7cx4 | ||||||
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Title | Cryo-EM structure of the Evatanepag-bound EP2-Gs complex | ||||||
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![]() | MEMBRANE PROTEIN / GPCR / EP2 / Complex / Evatanepag | ||||||
Function / homology | ![]() prostaglandin E receptor activity / Prostanoid ligand receptors / response to nematode / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway ...prostaglandin E receptor activity / Prostanoid ligand receptors / response to nematode / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / trans-Golgi network membrane / response to progesterone / G-protein beta/gamma-subunit complex binding / bone development / 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 / cognition / platelet aggregation / 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 / sensory perception of smell / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / positive regulation of cold-induced thermogenesis / phospholipase C-activating G protein-coupled receptor signaling pathway / regulation of cell population proliferation / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / response to lipopolysaccharide / inflammatory response / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | ![]() synthetic construct (others) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | ||||||
![]() | Qu, C. / Mao, C. / Xiao, P. / Shen, Q. / Zhong, Y. / Yang, F. / Shen, D. / Tao, X. / Zhang, H. / Yan, X. ...Qu, C. / Mao, C. / Xiao, P. / Shen, Q. / Zhong, Y. / Yang, F. / Shen, D. / Tao, X. / Zhang, H. / Yan, X. / Zhao, R. / He, J. / Guan, Y. / Zhang, C. / Hou, G. / Zhang, P. / Yu, X. / Guan, Y. / Sun, J. / Zhang, Y. | ||||||
![]() | ![]() Title: Ligand recognition, unconventional activation, and G protein coupling of the prostaglandin E receptor EP2 subtype. Authors: Changxiu Qu / Chunyou Mao / Peng Xiao / Qingya Shen / Ya-Ni Zhong / Fan Yang / Dan-Dan Shen / Xiaona Tao / Huibing Zhang / Xu Yan / Ru-Jia Zhao / Junyan He / Ying Guan / Chao Zhang / Guihua ...Authors: Changxiu Qu / Chunyou Mao / Peng Xiao / Qingya Shen / Ya-Ni Zhong / Fan Yang / Dan-Dan Shen / Xiaona Tao / Huibing Zhang / Xu Yan / Ru-Jia Zhao / Junyan He / Ying Guan / Chao Zhang / Guihua Hou / Peng-Ju Zhang / Guige Hou / Zijian Li / Xiao Yu / Ren-Jie Chai / You-Fei Guan / Jin-Peng Sun / Yan Zhang / ![]() Abstract: Selective modulation of the heterotrimeric G protein α S subunit-coupled prostaglandin E (PGE) receptor EP2 subtype is a promising therapeutic strategy for osteoporosis, ocular hypertension, ...Selective modulation of the heterotrimeric G protein α S subunit-coupled prostaglandin E (PGE) receptor EP2 subtype is a promising therapeutic strategy for osteoporosis, ocular hypertension, neurodegenerative diseases, and cardiovascular disorders. Here, we report the cryo-electron microscopy structure of the EP2-G complex with its endogenous agonist PGE and two synthesized agonists, taprenepag and evatanepag (CP-533536). These structures revealed distinct features of EP2 within the EP receptor family in terms of its unconventional receptor activation and G protein coupling mechanisms, including activation in the absence of a typical W "toggle switch" and coupling to G via helix 8. Moreover, inspection of the agonist-bound EP2 structures uncovered key motifs governing ligand selectivity. Our study provides important knowledge for agonist recognition and activation mechanisms of EP2 and will facilitate the rational design of drugs targeting the PGE signaling system. | ||||||
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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 | ![]() | 191.3 KB | Display | ![]() |
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PDB format | ![]() | 151.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 844.5 KB | Display | ![]() |
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Full document | ![]() | 854.2 KB | Display | |
Data in XML | ![]() | 36.4 KB | Display | |
Data in CIF | ![]() | 55.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 30491MC ![]() 7cx2C ![]() 7cx3C 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
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG
#2: Protein | Mass: 45683.434 Da / Num. of mol.: 1 Mutation: S54N, G226A, E268A, N271K, K274D, R280K, T284D, I285T Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#3: Protein | Mass: 39489.160 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#4: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Protein / Antibody / Non-polymers , 3 types, 3 molecules RN![](data/chem/img/GM9.gif)
![](data/chem/img/GM9.gif)
#1: Protein | Mass: 39800.430 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#5: Antibody | Mass: 13885.439 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: ![]() ![]() |
#6: Chemical | ChemComp-GM9 / |
-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 |
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Sample preparation
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||
Specimen | Conc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid type: Quantifoil | ||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / 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 / Nominal magnification: 29000 X / Calibrated magnification: 49310 X / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 64 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 2514 |
Image scans | Movie frames/image: 40 |
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Processing
Software | Name: PHENIX / Version: 1.16_3549: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1836927 | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 238945 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | PDB-ID: 7CFM | ||||||||||||||||||||||||
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