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Yorodumi- PDB-9jfk: Cryo-EM structure of [Pen5]-urotensin (4-11)-bounded human Uroten... -
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Basic information
| Entry | Database: PDB / ID: 9jfk | ||||||
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| Title | Cryo-EM structure of [Pen5]-urotensin (4-11)-bounded human Urotensin receptor (UTS2R)-Gq complex | ||||||
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Keywords | SIGNALING PROTEIN / Cryo-EM / GPCR / Urotensin receptor / UTS2R / Gq / agonist / [Pen5]-urotensin (4-11) / complex | ||||||
| Function / homology | Function and homology informationurotensin II receptor activity / blood circulation / neuropeptide signaling pathway / Peptide ligand-binding receptors / blood vessel diameter maintenance / G protein-coupled receptor activity / regulation of blood pressure / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta ...urotensin II receptor activity / blood circulation / neuropeptide signaling pathway / Peptide ligand-binding receptors / blood vessel diameter maintenance / G protein-coupled receptor activity / regulation of blood pressure / 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 / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / G-protein beta-subunit binding / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / GTPase binding / Ca2+ pathway / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / 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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.23 Å | ||||||
Authors | Xu, H.E. / You, C. / Gao, T. / Duan, J. | ||||||
| Funding support | China, 1items
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Citation | Journal: J Biol Chem / Year: 2025Title: Structural insights into hormone recognition and G-protein coupling of the urotensin-II receptor. Authors: Tianyu Gao / Chongzhao You / Yinglong Cao / Xiaofang Xu / Qingning Yuan / Shiyi Shen / H Eric Xu / Jia Duan / ![]() Abstract: Urotensin-II (U-II) is a potent vasoconstrictor peptide that interacts with the human urotensin-II receptor (UTR), a class A G protein-coupled receptor (GPCR) that primarily couples with G proteins. ...Urotensin-II (U-II) is a potent vasoconstrictor peptide that interacts with the human urotensin-II receptor (UTR), a class A G protein-coupled receptor (GPCR) that primarily couples with G proteins. In this study, we present the cryo-electron microscopy structure of the miniG-coupled UTR bound to the potent UTR agonist P5U, providing insights into unique ligand recognition and activation mechanisms. Unlike typical linear peptides, the cyclic structure of P5U engages the receptor's transmembrane domains through key side chain interactions involving residues F6, W7, K8, and Y9, which are crucial for receptor activation. Comparative analysis with somatostatin receptors (SSTRs) reveals distinct ligand specificity, driven by variations in side chain composition. Notably, we identify F274 as the toggle switch residue in UTR, in contrast to the classical W seen in other GPCRs. Our findings elucidate the structural basis for UTR's G coupling specificity, highlighting unique Gα interactions. This study advances the understanding of U-II signaling and offers a foundation for developing selective UTR modulators, with potential therapeutic implications for cardiovascular diseases linked to dysregulated U-II activity. | ||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9jfk.cif.gz | 214.5 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9jfk.ent.gz | 163.9 KB | Display | PDB format |
| PDBx/mmJSON format | 9jfk.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jf/9jfk ftp://data.pdbj.org/pub/pdb/validation_reports/jf/9jfk | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 61433MC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-Guanine nucleotide-binding protein ... , 2 types, 2 molecules AD
| #1: Protein | Mass: 37915.496 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 |
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| #3: Protein | Mass: 7729.947 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 |
-Protein , 2 types, 2 molecules BR
| #2: Protein | Mass: 28084.832 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Trichoplusia ni (cabbage looper) |
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| #5: Protein | Mass: 37857.465 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: UTS2R, GPR14 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9UKP6 |
-Antibody / Protein/peptide / Non-polymers , 3 types, 4 molecules NC

| #4: Antibody | Mass: 13885.439 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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| #6: Protein/peptide | Mass: 1092.310 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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-Details
| Has ligand of interest | Y |
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| Has protein modification | Y |
-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
| Component | Name: Cryo-EM structure of [Pen5]-urotensin (4-11)-bounded human Urotensin receptor (UTS2R)-Gq complex Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT |
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| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: Trichoplusia ni (cabbage looper) |
| Buffer solution | pH: 7.4 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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| Microscopy | Model: FEI TALOS ARCTICA |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 30000 nm / Nominal defocus min: 5000 nm |
| Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.23 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 168270 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refinement | Highest resolution: 3.23 Å Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS) | ||||||||||||||||||||||||
| Refine LS restraints |
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About Yorodumi



Homo sapiens (human)

China, 1items
Citation
PDBj

























Trichoplusia ni (cabbage looper)

FIELD EMISSION GUN