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- PDB-9nou: Human sweet taste receptor (TAS1R2 + TAS1R3) VFT domains from the... -

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Basic information

Entry
Database: PDB / ID: 9nou
TitleHuman sweet taste receptor (TAS1R2 + TAS1R3) VFT domains from the combined datasets
Components
  • Taste receptor type 1 member 2
  • Taste receptor type 1 member 3
KeywordsMEMBRANE PROTEIN / Sweet / taste / receptor / GPCR / TAS1R2 / TAS1R3 / T1R2 / T1R3
Function / homology
Function and homology information


sweet taste receptor complex / detection of chemical stimulus involved in sensory perception of sweet taste / sweet taste receptor activity / taste receptor activity / sensory perception of umami taste / sensory perception of sweet taste / Class C/3 (Metabotropic glutamate/pheromone receptors) / positive regulation of cytokinesis / G protein-coupled receptor activity / Sensory perception of sweet, bitter, and umami (glutamate) taste ...sweet taste receptor complex / detection of chemical stimulus involved in sensory perception of sweet taste / sweet taste receptor activity / taste receptor activity / sensory perception of umami taste / sensory perception of sweet taste / Class C/3 (Metabotropic glutamate/pheromone receptors) / positive regulation of cytokinesis / G protein-coupled receptor activity / Sensory perception of sweet, bitter, and umami (glutamate) taste / G alpha (i) signalling events / receptor complex / G protein-coupled receptor signaling pathway / Golgi apparatus / membrane / plasma membrane
Similarity search - Function
GPCR, family 3, extracellular calcium-sensing receptor-related / G-protein coupled receptors family 3 signature 2. / GPCR, family 3, nine cysteines domain / GPCR, family 3, nine cysteines domain superfamily / Nine Cysteines Domain of family 3 GPCR / GPCR, family 3, conserved site / GPCR, family 3 / G-protein coupled receptors family 3 profile. / GPCR family 3, C-terminal / 7 transmembrane sweet-taste receptor of 3 GCPR ...GPCR, family 3, extracellular calcium-sensing receptor-related / G-protein coupled receptors family 3 signature 2. / GPCR, family 3, nine cysteines domain / GPCR, family 3, nine cysteines domain superfamily / Nine Cysteines Domain of family 3 GPCR / GPCR, family 3, conserved site / GPCR, family 3 / G-protein coupled receptors family 3 profile. / GPCR family 3, C-terminal / 7 transmembrane sweet-taste receptor of 3 GCPR / Receptor, ligand binding region / Receptor family ligand binding region / Periplasmic binding protein-like I
Similarity search - Domain/homology
Taste receptor type 1 member 3 / Taste receptor type 1 member 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å
AuthorsJuen, Z. / Lu, Z. / Yu, R. / Chang, A.N. / Wang, B. / Fitzpatrick, A.W.P. / Zuker, C.S.
Funding support United States, 1items
OrganizationGrant numberCountry
Howard Hughes Medical Institute (HHMI) United States
CitationJournal: Cell / Year: 2025
Title: The structure of human sweetness.
Authors: Zhang Juen / Zhengyuan Lu / Ruihuan Yu / Andrew N Chang / Brian Wang / Anthony W P Fitzpatrick / Charles S Zuker /
Abstract: In humans, the detection and ultimately the perception of sweetness begin in the oral cavity, where taste receptor cells (TRCs) dedicated to sweet-sensing interact with sugars, artificial sweeteners, ...In humans, the detection and ultimately the perception of sweetness begin in the oral cavity, where taste receptor cells (TRCs) dedicated to sweet-sensing interact with sugars, artificial sweeteners, and other sweet-tasting chemicals. Human sweet TRCs express on their cell surface a sweet receptor that initiates the cascade of signaling events responsible for our strong attraction to sweet stimuli. Here, we describe the cryo-electron microscopy (cryo-EM) structure of the human sweet receptor bound to two of the most widely used artificial sweeteners-sucralose and aspartame. Our results reveal the structural basis for sweet detection, provide insights into how a single receptor mediates all our responses to such a wide range of sweet-tasting compounds, and open up unique possibilities for designing a generation of taste modulators informed by the structure of the human receptor.
History
DepositionMar 10, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 14, 2025Provider: repository / Type: Initial release
Revision 1.1May 21, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name / _em_admin.last_update

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
B: Taste receptor type 1 member 3
A: Taste receptor type 1 member 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)121,42317
Polymers118,1052
Non-polymers3,31815
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein Taste receptor type 1 member 3 / Sweet taste receptor T1R3


Mass: 58379.551 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TAS1R3, T1R3, TR3 / Production host: Homo sapiens (human) / References: UniProt: Q7RTX0
#2: Protein Taste receptor type 1 member 2 / G-protein coupled receptor 71 / Sweet taste receptor T1R2


Mass: 59725.098 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TAS1R2, GPR71, T1R2, TR2 / Production host: Homo sapiens (human) / References: UniProt: Q8TE23
#3: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 15 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Human sweet taste receptor (TAS1R2 + TAS1R3) VFT domains
Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1200 nm
Image recordingElectron dose: 59 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

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Processing

EM softwareName: PHENIX / Category: model refinement
CTF correctionType: NONE
3D reconstructionResolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 776095 / Symmetry type: POINT
RefinementHighest resolution: 2.8 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0047804
ELECTRON MICROSCOPYf_angle_d0.57110609
ELECTRON MICROSCOPYf_dihedral_angle_d6.6011321
ELECTRON MICROSCOPYf_chiral_restr0.0471232
ELECTRON MICROSCOPYf_plane_restr0.0041338

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