[English] 日本語
Yorodumi- PDB-8gda: Cryo-EM Structure of the Prostaglandin E2 Receptor 4 Coupled to G... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8gda | ||||||
---|---|---|---|---|---|---|---|
Title | Cryo-EM Structure of the Prostaglandin E2 Receptor 4 Coupled to G Protein | ||||||
Components |
| ||||||
Keywords | SIGNALING PROTEIN / GPCR complex | ||||||
Function / homology | Function and homology information 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 / positive regulation of cAMP-mediated signaling / response to mechanical stimulus / adenylate cyclase-activating adrenergic receptor signaling pathway / JNK cascade / ERK1 and ERK2 cascade / activation of adenylate cyclase activity / adenylate cyclase activator activity / trans-Golgi network membrane / positive regulation of cytokine production / Olfactory Signaling Pathway / G-protein beta/gamma-subunit complex binding / Activation of the phototransduction cascade / bone development / 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 / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / cognition / platelet aggregation / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / positive regulation of GTPase activity / Vasopressin regulates renal water homeostasis via Aquaporins / negative regulation of inflammatory response / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / positive regulation of inflammatory response / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to mechanical stimulus / 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 / 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) / retina development in camera-type eye / GTPase binding / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cold-induced thermogenesis / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / response to lipopolysaccharide / Extra-nuclear estrogen signaling / immune response / 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 / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Lama glama (llama) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
Authors | Shenming, H. / Mengyao, X. / Lei, L. / Jiangqian, M. / Sheng, C. / Jinpeng, S. | ||||||
Funding support | China, 1items
| ||||||
Citation | Journal: Proc Natl Acad Sci U S A / Year: 2023 Title: Single hormone or synthetic agonist induces G/G coupling selectivity of EP receptors via distinct binding modes and propagating paths. Authors: Shen-Ming Huang / Meng-Yao Xiong / Lei Liu / Jianqiang Mu / Ming-Wei Wang / Ying-Li Jia / Kui Cai / Lu Tie / Chao Zhang / Sheng Cao / Xin Wen / Jia-Le Wang / Sheng-Chao Guo / Yu Li / Chang- ...Authors: Shen-Ming Huang / Meng-Yao Xiong / Lei Liu / Jianqiang Mu / Ming-Wei Wang / Ying-Li Jia / Kui Cai / Lu Tie / Chao Zhang / Sheng Cao / Xin Wen / Jia-Le Wang / Sheng-Chao Guo / Yu Li / Chang-Xiu Qu / Qing-Tao He / Bo-Yang Cai / Chenyang Xue / Shiyi Gan / Yihe Xie / Xin Cong / Zhao Yang / Wei Kong / Shuo Li / Zijian Li / Peng Xiao / Fan Yang / Xiao Yu / You-Fei Guan / Xiaoyan Zhang / Zhongmin Liu / Bao-Xue Yang / Yang Du / Jin-Peng Sun / Abstract: To accomplish concerted physiological reactions, nature has diversified functions of a single hormone at at least two primary levels: 1) Different receptors recognize the same hormone, and 2) ...To accomplish concerted physiological reactions, nature has diversified functions of a single hormone at at least two primary levels: 1) Different receptors recognize the same hormone, and 2) different cellular effectors couple to the same hormone-receptor pair [R.P. Xiao, , re15 (2001); L. Hein, J. D. Altman, B.K. Kobilka, , 181-184 (1999); Y. Daaka, L. M. Luttrell, R. J. Lefkowitz, , 88-91 (1997)]. Not only these questions lie in the heart of hormone actions and receptor signaling but also dissecting mechanisms underlying these questions could offer therapeutic routes for refractory diseases, such as kidney injury (KI) or X-linked nephrogenic diabetes insipidus (NDI). Here, we identified that G-biased signaling, but not G activation downstream of EP4, showed beneficial effects for both KI and NDI treatments. Notably, by solving Cryo-electron microscope (cryo-EM) structures of EP3-G, EP4-G, and EP4-G in complex with endogenous prostaglandin E (PGE)or two synthetic agonists and comparing with PGE-EP2-G structures, we found that unique primary sequences of prostaglandin E2 receptor (EP) receptors and distinct conformational states of the EP4 ligand pocket govern the G/G transducer coupling selectivity through different structural propagation paths, especially via TM6 and TM7, to generate selective cytoplasmic structural features. In particular, the orientation of the PGE ω-chain and two distinct pockets encompassing agonist L902688 of EP4 were differentiated by their G/G coupling ability. Further, we identified common and distinct features of cytoplasmic side of EP receptors for G/G coupling and provide a structural basis for selective and biased agonist design of EP4 with therapeutic potential. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8gda.cif.gz | 239.3 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8gda.ent.gz | 172.7 KB | Display | PDB format |
PDBx/mmJSON format | 8gda.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gd/8gda ftp://data.pdbj.org/pub/pdb/validation_reports/gd/8gda | HTTPS FTP |
---|
-Related structure data
Related structure data | 29944MC 8gcmC 8gcpC 8gd9C 8gdbC 8gdcC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG
#1: Protein | Mass: 45727.441 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAS, GNAS1, GSP / Plasmid: pFastBac1-HM / Production host: Baculovirus expression vector pFastBac1-HM / References: UniProt: P63092 |
---|---|
#2: Protein | Mass: 38458.012 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Plasmid: pFastBac1-HM / Production host: Baculovirus expression vector pFastBac1-HM / References: UniProt: P62873 |
#3: Protein | Mass: 12104.898 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: mRhiFer1_005810 / Plasmid: pFastBac1-HM / Production host: Baculovirus expression vector pFastBac1-HM / References: UniProt: A0A7J7XNR4 |
-Antibody / Protein / Non-polymers , 3 types, 3 molecules NR
#4: Antibody | Mass: 13885.439 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Lama glama (llama) / Production host: unidentified (others) |
---|---|
#5: Protein | Mass: 53173.336 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PTGER4, PTGER2 / Plasmid: pFastBac1-HM / Production host: Baculovirus expression vector pFastBac1-HM / References: UniProt: P35408 |
#6: Chemical | ChemComp-YZV / ( |
-Details
Has ligand of interest | Y |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Prostaglandin E Receptor EP4 Coupled to G Protein / Type: COMPLEX / Entity ID: #1-#5 / Source: MULTIPLE SOURCES |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Baculovirus expression vector pFastBac1-HM |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: OTHER / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: OTHER / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 25 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
---|---|
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 279955 / Symmetry type: POINT |