+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-30491 | |||||||||
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Title | Cryo-EM structure of the Evatanepag-bound EP2-Gs complex | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information prostaglandin E receptor activity / Prostanoid ligand receptors / response to nematode / response to progesterone / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors ...prostaglandin E receptor activity / Prostanoid ligand receptors / response to nematode / response to progesterone / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / 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 / G beta:gamma signalling through CDC42 / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / 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 / regulation of cell population proliferation / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / 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 / response to lipopolysaccharide / cell population proliferation / Extra-nuclear estrogen signaling / inflammatory response / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / signal transduction / extracellular exosome / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / synthetic construct (others) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
Authors | 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 / Sun J / Zhang Y | |||||||||
Citation | Journal: Sci Adv / Year: 2021 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. | |||||||||
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_30491.map.gz | 18 MB | EMDB map data format | |
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Header (meta data) | emd-30491-v30.xml emd-30491.xml | 19.6 KB 19.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_30491_fsc.xml | 6.7 KB | Display | FSC data file |
Images | emd_30491.png | 68.5 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30491 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30491 | HTTPS FTP |
-Validation report
Summary document | emd_30491_validation.pdf.gz | 399.9 KB | Display | EMDB validaton report |
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Full document | emd_30491_full_validation.pdf.gz | 399.5 KB | Display | |
Data in XML | emd_30491_validation.xml.gz | 9.5 KB | Display | |
Data in CIF | emd_30491_validation.cif.gz | 12.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30491 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30491 | HTTPS FTP |
-Related structure data
Related structure data | 7cx4MC 7cx2C 7cx3C 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_30491.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.014 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
+Entire : PGE2-bound EP2-Gs complex
+Supramolecule #1: PGE2-bound EP2-Gs complex
+Supramolecule #2: EP2
+Supramolecule #3: Nb35
+Supramolecule #4: Gs
+Macromolecule #1: Prostaglandin E2 receptor EP2 subtype
+Macromolecule #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #5: Nanobody-35
+Macromolecule #6: 2-[3-[[(4-~{tert}-butylphenyl)methyl-pyridin-3-ylsulfonyl-amino]m...
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 5.0 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil / Material: GOLD / Support film - Material: CARBON / Support film - topology: HOLEY |
Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number real images: 2514 / Average electron dose: 64.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated magnification: 49310 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal magnification: 29000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |