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- EMDB-49618: Human sweet taste receptor (TAS1R2 + TAS1R3) VFT domains bound to... -

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Basic information

Entry
Database: EMDB / ID: EMD-49618
TitleHuman sweet taste receptor (TAS1R2 + TAS1R3) VFT domains bound to sucralose
Map data
Sample
  • Complex: Human sweet taste receptor (TAS1R2 + TAS1R3) VFT domains bound to sucralose
    • Protein or peptide: Taste receptor type 1 member 3
    • Protein or peptide: Taste receptor type 1 member 2
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsSweet / taste / receptor / GPCR / TAS1R2 / TAS1R3 / T1R2 / T1R3 / MEMBRANE PROTEIN
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)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsJuen Z / Lu Z / Yu R / Chang AN / Wang B / Fitzpatrick AWP / Zuker CS
Funding support United States, 1 items
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, 2025-
Header (metadata) releaseMay 14, 2025-
Map releaseMay 14, 2025-
UpdateMay 21, 2025-
Current statusMay 21, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_49618.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.82 Å/pix.
x 440 pix.
= 362.12 Å
0.82 Å/pix.
x 440 pix.
= 362.12 Å
0.82 Å/pix.
x 440 pix.
= 362.12 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.823 Å
Density
Contour LevelBy AUTHOR: 0.178
Minimum - Maximum-0.47051132 - 0.92621624
Average (Standard dev.)-0.000025928877 (±0.02052558)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions440440440
Spacing440440440
CellA=B=C: 362.12 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_49618_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_49618_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_49618_half_map_2.map
Projections & Slices
AxesZYX

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Slices (1/2)
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Sample components

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Entire : Human sweet taste receptor (TAS1R2 + TAS1R3) VFT domains bound to...

EntireName: Human sweet taste receptor (TAS1R2 + TAS1R3) VFT domains bound to sucralose
Components
  • Complex: Human sweet taste receptor (TAS1R2 + TAS1R3) VFT domains bound to sucralose
    • Protein or peptide: Taste receptor type 1 member 3
    • Protein or peptide: Taste receptor type 1 member 2
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: Human sweet taste receptor (TAS1R2 + TAS1R3) VFT domains bound to...

SupramoleculeName: Human sweet taste receptor (TAS1R2 + TAS1R3) VFT domains bound to sucralose
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Taste receptor type 1 member 3

MacromoleculeName: Taste receptor type 1 member 3 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 58.379551 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MKTIIALSYI FCLVFADYKD DDDKAAAAPL CLSQQLRMKG DYVLGGLFPL GEAEEAGLRS RTRPSSPVCT RFSSNGLLWA LAMKMAVEE INNKSDLLPG LRLGYDLFDT CSEPVVAMKP SLMFLAKAGS RDIAAYCNYT QYQPRVLAVI GPHSSELAMV T GKFFSFFL ...String:
MKTIIALSYI FCLVFADYKD DDDKAAAAPL CLSQQLRMKG DYVLGGLFPL GEAEEAGLRS RTRPSSPVCT RFSSNGLLWA LAMKMAVEE INNKSDLLPG LRLGYDLFDT CSEPVVAMKP SLMFLAKAGS RDIAAYCNYT QYQPRVLAVI GPHSSELAMV T GKFFSFFL MPQVSYGASM ELLSARETFP SFFRTVPSDR VQLTAAAELL QEFGWNWVAA LGSDDEYGRQ GLSIFSALAA AR GICIAHE GLVPLPRADD SRLGKVQDVL HQVNQSSVQV VLLFASVHAA HALFNYSISS RLSPKVWVAS EAWLTSDLVM GLP GMAQMG TVLGFLQRGA QLHEFPQYVK THLALATDPA FCSALGEREQ GLEEDVVGQR CPQCDCITLQ NVSAGLNHHQ TFSV YAAVY SVAQALHNTL QCNASGCPAQ DPVKPWQLLE NMYNLTFHVG GLPLRFDSSG NVDMEYDLKL WVWQGSVPRL HDVGR FNGS LRTERLKIRW HTSDNQKPVS RCSRQCQEGQ VRRVKGFHSC CYDC

UniProtKB: Taste receptor type 1 member 3

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Macromolecule #2: Taste receptor type 1 member 2

MacromoleculeName: Taste receptor type 1 member 2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 60.070512 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MKTIIALSYI FCLVFAYPYD VPDYAAAAEP AENSDFYLPG DYLLGGLFSL HANMKGIVHL NFLQVPMCKE YEVKVIGYNL MQAMRFAVE EINNDSSLLP GVLLGYEIVD VCYISNNVQP VLYFLAHEDN LLPIQEDYSN YISRVVAVIG PDNSESVMTV A NFLSLFLL ...String:
MKTIIALSYI FCLVFAYPYD VPDYAAAAEP AENSDFYLPG DYLLGGLFSL HANMKGIVHL NFLQVPMCKE YEVKVIGYNL MQAMRFAVE EINNDSSLLP GVLLGYEIVD VCYISNNVQP VLYFLAHEDN LLPIQEDYSN YISRVVAVIG PDNSESVMTV A NFLSLFLL PQITYSAISD ELRDKVRFPA LLRTTPSADH HIEAMVQLML HFRWNWIIVL VSSDTYGRDN GQLLGERVAR RD ICIAFQE TLPTLQPNQN MTSEERQRLV TIVDKLQQST ARVVVVFSPD LTLYHFFNEV LRQNFTGAVW IASESWAIDP VLH NLTELR HLGTFLGITI QSVPIPGFSE FREWGPQAGP PPLSRTSQSY TCNQECDNCL NATLSFNTIL RLSGERVVYS VYSA VYAVA HALHSLLGCD KSTCTKRVVY PWQLLEEIWK VNFTLLDHQI FFDPQGDVAL HLEIVQWQWD RSQNPFQSVA SYYPL QRQL KNIQDISWHT INNTIPMSMC SKRCQSGQKK KPVGIHVCCF ECI

UniProtKB: Taste receptor type 1 member 2

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Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 15 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 59.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: NONE
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 20540
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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