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- PDB-7d7m: Cryo-EM Structure of the Prostaglandin E Receptor EP4 Coupled to ... -
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Basic information
Entry | Database: PDB / ID: 7d7m | ||||||||||||||||||
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Title | Cryo-EM Structure of the Prostaglandin E Receptor EP4 Coupled to G Protein | ||||||||||||||||||
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![]() | MEMBRANE PROTEIN / prostaglandin E receptor / EP4 / GPCR / G protein | ||||||||||||||||||
Function / homology | ![]() negative regulation of eosinophil extravasation / prostaglandin E receptor activity / Prostanoid ligand receptors / negative regulation of integrin activation / response to nematode / T-helper cell differentiation / regulation of stress fiber assembly / negative regulation of cytokine production / PKA activation in glucagon signalling / hair follicle placode formation ...negative regulation of eosinophil extravasation / prostaglandin E receptor activity / Prostanoid ligand receptors / negative regulation of integrin activation / response to nematode / T-helper cell differentiation / regulation of stress fiber assembly / negative regulation of cytokine production / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / regulation of ossification / intracellular transport / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / response to mechanical stimulus / JNK cascade / adenylate cyclase activator activity / ERK1 and ERK2 cascade / trans-Golgi network membrane / positive regulation of cytokine production / G-protein beta/gamma-subunit complex binding / bone development / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 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 / negative regulation of inflammatory response / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / positive regulation of inflammatory response / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to mechanical stimulus / 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 / 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 / cell population proliferation / response to lipopolysaccharide / Extra-nuclear estrogen signaling / inflammatory response / immune 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 / cytosol / cytoplasm Similarity search - Function | ||||||||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||||||||||||||
![]() | Nojima, S. / Fujita, Y. / Kimura, T.K. / Nomura, N. / Suno, R. / Morimoto, K. / Yamamoto, M. / Noda, T. / Iwata, S. / Shigematsu, H. / Kobayashi, T. | ||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM Structure of the Prostaglandin E Receptor EP4 Coupled to G Protein. Authors: Shingo Nojima / Yoko Fujita / Kanako Terakado Kimura / Norimichi Nomura / Ryoji Suno / Kazushi Morimoto / Masaki Yamamoto / Takeshi Noda / So Iwata / Hideki Shigematsu / Takuya Kobayashi / ![]() Abstract: Prostaglandin E receptor EP4, a class A G protein-coupled receptor (GPCR), is a common drug target in various disorders, such as acute decompensated heart failure and ulcerative colitis. Here, we ...Prostaglandin E receptor EP4, a class A G protein-coupled receptor (GPCR), is a common drug target in various disorders, such as acute decompensated heart failure and ulcerative colitis. Here, we report the cryoelectron microscopy (cryo-EM) structure of the EP4-heterotrimeric G protein (Gs) complex with the endogenous ligand at a global resolution of 3.3 Å. In this structure, compared with that in the inactive EP4 structure, the sixth transmembrane domain is shifted outward on the intracellular side, although the shift is smaller than that in other class A GPCRs bound to Gs. Instead, the C-terminal helix of Gs is inserted toward TM2 of EP4, and the conserved C-terminal hook structure formsthe extended state. These structural features are formed by the conserved residues in prostanoid receptors (Phe54 and Trp327). These findings may be important for the thorough understanding of the G protein-binding mechanism of EP4 and other prostanoid receptors. | ||||||||||||||||||
History |
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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 | ![]() | 200.1 KB | Display | ![]() |
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PDB format | ![]() | 153.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 30608MC 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 BCD
#2: Protein | Mass: 37728.152 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#4: Protein | Mass: 29014.750 Da / Num. of mol.: 1 Mutation: 65 to 203, 255 to 264 deletion G49D, E50N, L63Y, A249D, S252D, I372A and V375I Source method: isolated from a genetically manipulated source Details: residues from 65 to 203, residues from 255 to 264 were deleted Source: (gene. exp.) ![]() ![]() ![]() |
-Protein / Antibody / Non-polymers , 3 types, 3 molecules AE![](data/chem/img/P2E.gif)
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#1: Protein | Mass: 36953.453 Da / Num. of mol.: 1 / Mutation: N7Q, N177Q, 218-259 deletion Source method: isolated from a genetically manipulated source Details: residues from 218 to 259 were deleted / Source: (gene. exp.) ![]() ![]() ![]() |
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#5: Antibody | Mass: 14680.293 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: The C-terminal "ENLYFQ" of sample sequence is a cleavaged TEV protease recognition sequence. Source: (gene. exp.) ![]() ![]() ![]() |
#6: Chemical | ChemComp-P2E / ( |
-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: 2D ARRAY / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Molecular weight | Value: 0.12 MDa / Experimental value: YES | |||||||||||||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | |||||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 8.4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||||||||||||
Specimen support | Details: 10 mA / Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R0.6/1 | |||||||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 281 K / Details: Blot Force 10, Blot Time 3.5 sec, 3 microL apply |
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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: 105000 X / Nominal defocus max: 1800 nm / Nominal defocus min: 600 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: ZEMLIN TABLEAU |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Residual tilt: 0.01 mradians |
Image recording | Average exposure time: 1.83 sec. / Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 5743 |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 25 eV |
Image scans | Sampling size: 5 µm / Width: 4092 / Height: 5760 |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING ONLY | |||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 2796263 | |||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 178217 / Algorithm: FOURIER SPACE / Num. of class averages: 1 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | |||||||||||||||||||||||||||||||||||||||||||||
Atomic model building |
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