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Yorodumi- PDB-9w0q: Cryo-EM structure of T2R14 in complex with tangeretin and heterot... -
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Open data
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Basic information
| Entry | Database: PDB / ID: 9w0q | |||||||||||||||||||||
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| Title | Cryo-EM structure of T2R14 in complex with tangeretin and heterotrimeric G protein | |||||||||||||||||||||
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Keywords | MEMBRANE PROTEIN / G protein-coupled receptor / Bitter taste receptor 14 / ligand binding / signal transduction | |||||||||||||||||||||
| Function / homology | Function and homology informationbitter taste receptor activity / taste receptor activity / detection of chemical stimulus involved in sensory perception of bitter taste / Class C/3 (Metabotropic glutamate/pheromone receptors) / regulation of eating behavior / adenylate cyclase inhibitor activity / T cell migration / positive regulation of protein localization to cell cortex / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway ...bitter taste receptor activity / taste receptor activity / detection of chemical stimulus involved in sensory perception of bitter taste / Class C/3 (Metabotropic glutamate/pheromone receptors) / regulation of eating behavior / adenylate cyclase inhibitor activity / T cell migration / positive regulation of protein localization to cell cortex / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / cellular response to forskolin / regulation of mitotic spindle organization / mast cell degranulation / chemokine-mediated signaling pathway / electron transport chain / neuropeptide signaling pathway / Regulation of insulin secretion / response to prostaglandin E / positive regulation of cholesterol biosynthetic process / G protein-coupled receptor binding / response to peptide hormone / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / GDP binding / G beta:gamma signalling through BTK / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / 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 / G beta:gamma signalling through PI3Kgamma / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / heterotrimeric G-protein complex / Inactivation, recovery and regulation of the phototransduction cascade / G alpha (12/13) signalling events / G-protein beta-subunit binding / extracellular vesicle / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / GTPase binding / G protein activity / midbody / Ca2+ pathway / cell cortex / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / ciliary basal body / G alpha (s) signalling events / G alpha (q) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / Ras protein signal transduction / electron transfer activity / periplasmic space / Extra-nuclear estrogen signaling / iron ion binding / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / GTPase activity / heme binding / centrosome / synapse / GTP binding / protein-containing complex binding / magnesium ion binding / signal transduction / extracellular exosome / membrane / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||||||||||||||
| Biological species | Homo sapiens (human)![]() | |||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||||||||||||||
Authors | Tan, Q. / Yu, Y. / Han, X. / Zhao, Q. / Wu, B. | |||||||||||||||||||||
| Funding support | China, 4items
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Citation | Journal: Nat Struct Mol Biol / Year: 2026Title: Ligand binding modes of the bitter taste receptor T2R14 and T2R46. Authors: Qiuxiang Tan / Yu Yu / Xuteng Han / Kezhen Liu / Shuo Han / Mu Wang / Yuan Wei / Yingrong Zhu / Qiuru Chen / Limin Ma / Cuiying Yi / Xiaojing Chu / Beili Wu / Qiang Zhao / ![]() Abstract: Bitter taste receptors (T2Rs) are considered attractive drug targets. However, the ligand recognition and selectivity of these receptors remain elusive, hampering their drug development. Here we ...Bitter taste receptors (T2Rs) are considered attractive drug targets. However, the ligand recognition and selectivity of these receptors remain elusive, hampering their drug development. Here we present seven structures of human T2R14 and T2R46 in apo or ligand-bound state. Combined with molecular docking and mutagenesis data, the structures reveal an extracellular ligand-binding site in T2R14 for most of its ligands, which is different from the intracellular binding site reported recently. In contrast, T2R46 exhibits a conserved binding pocket that accommodates various ligands with distinct interaction patterns. Furthermore, the second extracellular loop in T2R14 and T2R46 acts as a tethered agonist to potentially facilitate agonist response of these two receptors to the weak tastant agonists. These findings could accelerate drug discovery targeting T2Rs. | |||||||||||||||||||||
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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 | 9w0q.cif.gz | 173.9 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9w0q.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 9w0q.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/w0/9w0q ftp://data.pdbj.org/pub/pdb/validation_reports/w0/9w0q | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 65512MC ![]() 9w0pC ![]() 9w0rC ![]() 9w0sC ![]() 9w0tC ![]() 9w0uC ![]() 9w0wC 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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| 1 |
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Components
| #1: Protein | Mass: 40458.102 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1 / Production host: ![]() References: UniProt: P63096, Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement |
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| #2: Protein | Mass: 38744.371 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: ![]() |
| #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: ![]() |
| #4: Protein | Mass: 54569.516 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Homo sapiens (human)Gene: cybC, TAS2R14 / Production host: ![]() |
| #5: Chemical | ChemComp-A1EUI / Mass: 372.369 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H20O7 |
| Has ligand of interest | Y |
| Has protein modification | N |
-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: Ternary complex of T2R14 with G protein heterotrimeric Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT | ||||||||||||
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| Molecular weight | Value: 10 kDa/nm / Experimental value: YES | ||||||||||||
| Source (natural) |
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| Source (recombinant) | Organism: ![]() | ||||||||||||
| Buffer solution | pH: 7.5 | ||||||||||||
| Buffer component | Conc.: 2.8 mg/ml / Name: sodium chloride / Formula: 150mM | ||||||||||||
| Specimen | Conc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: This sample was monodisperse | ||||||||||||
| Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 298 K / Details: blot for 1s |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Tecnai F30 / Image courtesy: FEI Company |
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| Microscopy | Model: FEI TECNAI F30 |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1500 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / Alignment procedure: BASIC |
| Image recording | Average exposure time: 2 sec. / Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of grids imaged: 2 / Num. of real images: 9856 / Details: Images were collected in movie-mode |
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Processing
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| Image processing | Details: The selected images were 20eV using GIF-Quantum LS Imaging energy filter | ||||||||||||||||||||||||
| CTF correction | Type: NONE | ||||||||||||||||||||||||
| Particle selection | Num. of particles selected: 3399613 | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 883086 / Symmetry type: POINT | ||||||||||||||||||||||||
| Atomic model building | B value: 31.78 / Space: REAL | ||||||||||||||||||||||||
| Atomic model building | PDB-ID: 7x9a Accession code: 7x9a / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||
| Refinement | Highest resolution: 3.2 Å Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS) | ||||||||||||||||||||||||
| Refine LS restraints |
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Homo sapiens (human)

China, 4items
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FIELD EMISSION GUN
