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Yorodumi- PDB-8iq6: Cryo-EM structure of Latanoprost-bound prostaglandin-F2-alpha rec... -
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-Basic information
Entry | Database: PDB / ID: 8iq6 | ||||||
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Title | Cryo-EM structure of Latanoprost-bound prostaglandin-F2-alpha receptor-miniGq-Nb35 complex | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / GPCR / Complex / Prostaglandin receptor / Agonist | ||||||
Function / homology | Function and homology information prostaglandin F receptor activity / parturition / Prostanoid ligand receptors / cellular response to prostaglandin D stimulus / 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 F receptor activity / parturition / Prostanoid ligand receptors / cellular response to prostaglandin D stimulus / 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) / response to estradiol / GTPase binding / retina development in camera-type eye / 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 / positive regulation of cell population proliferation / protein-containing complex binding / positive regulation of gene expression / negative regulation of apoptotic process / signal transduction / extracellular exosome / extracellular region / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Vicugna pacos (alpaca) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | ||||||
Authors | Lv, X. / Gao, K. / Nie, J. / Zhang, X. / Zhang, S. / Ren, Y. / Li, Q. / Huang, J. / Liu, L. / Zhang, X. ...Lv, X. / Gao, K. / Nie, J. / Zhang, X. / Zhang, S. / Ren, Y. / Li, Q. / Huang, J. / Liu, L. / Zhang, X. / Sun, X. / Zhang, W. / Liu, X. | ||||||
Funding support | China, 1items
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Citation | Journal: Nat Commun / Year: 2023 Title: Structures of human prostaglandin F receptor reveal the mechanism of ligand and G protein selectivity. Authors: Xiuqing Lv / Kaixuan Gao / Jia Nie / Xin Zhang / Shuhao Zhang / Yinhang Ren / Xiaoou Sun / Qi Li / Jingrui Huang / Lijuan Liu / Xiaowen Zhang / Weishe Zhang / Xiangyu Liu / Abstract: Prostaglandins and their receptors regulate various physiological processes. Carboprost, an analog of prostaglandin F and an agonist for the prostaglandin F2-alpha receptor (FP receptor), is ...Prostaglandins and their receptors regulate various physiological processes. Carboprost, an analog of prostaglandin F and an agonist for the prostaglandin F2-alpha receptor (FP receptor), is clinically used to treat postpartum hemorrhage (PPH). However, off-target activation of closely related receptors such as the prostaglandin E receptor subtype EP3 (EP3 receptor) by carboprost results in side effects and limits the clinical application. Meanwhile, the FP receptor selective agonist latanoprost is not suitable to treat PPH due to its poor solubility and fast clearance. Here, we present two cryo-EM structures of the FP receptor bound to carboprost and latanoprost-FA (the free acid form of latanoprost) at 2.7 Å and 3.2 Å resolution, respectively. The structures reveal the molecular mechanism of FP receptor selectivity for both endogenous prostaglandins and clinical drugs, as well as the molecular mechanism of G protein coupling preference by the prostaglandin receptors. The structural information may guide the development of better prostaglandin drugs. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8iq6.cif.gz | 199.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8iq6.ent.gz | 147.9 KB | Display | PDB format |
PDBx/mmJSON format | 8iq6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8iq6_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 8iq6_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 8iq6_validation.xml.gz | 36 KB | Display | |
Data in CIF | 8iq6_validation.cif.gz | 53 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/iq/8iq6 ftp://data.pdbj.org/pub/pdb/validation_reports/iq/8iq6 | HTTPS FTP |
-Related structure data
Related structure data | 35658MC 8iq4C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG
#1: Protein | Mass: 28168.926 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAS, GNAS1, GSP / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63092 |
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#2: Protein | Mass: 39418.086 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P62873 |
#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P59768 |
-Antibody / Protein / Non-polymers , 3 types, 3 molecules NR
#4: Antibody | Mass: 14686.328 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Vicugna pacos (alpaca) / Production host: Escherichia coli (E. coli) |
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#5: Protein | Mass: 42909.363 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PTGFR / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P43088 |
#6: Chemical | ChemComp-7WT / |
-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 |
-Sample preparation
Component | Name: Cryo-EM structure of Latanoprost-bound prostaglandin-F2-alpha receptor-miniGq-Nb35 complex Type: COMPLEX / Entity ID: #1-#5 / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.45 |
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 |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 1100 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 132183 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 40.79 Å2 | ||||||||||||||||||||||||
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