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- EMDB-64485: The VFT domains of human sweet taste receptor TAS1R2 and TAS1R3 i... -

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Basic information

Entry
Database: EMDB / ID: EMD-64485
TitleThe VFT domains of human sweet taste receptor TAS1R2 and TAS1R3 in the apo state
Map data
Sample
  • Complex: heterodimer
    • Protein or peptide: Taste receptor type 1 member 2,Engineered red fluorescent protein mScarlet3
    • Protein or peptide: Taste receptor type 1 member 3,mNeonGreen
KeywordsGPCR / Taste / Tas1R2 / Tas1R3 / SIGNALING 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 / bioluminescence / G protein-coupled receptor activity ...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 / bioluminescence / 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 / Green fluorescent protein-related / Green fluorescent protein / Green fluorescent protein / Receptor, ligand binding region / Receptor family ligand binding region / Periplasmic binding protein-like I
Similarity search - Domain/homology
mNeonGreen / Taste receptor type 1 member 3 / Taste receptor type 1 member 2
Similarity search - Component
Biological speciesHomo sapiens (human) / Discosoma sp. (Sea anemone) (sea anemone) / Branchiostoma lanceolatum (amphioxus)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.18 Å
AuthorsShi ZJ / Xu WX / Yue XL / Wu LJ / Hua T / Liu ZJ
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Nature / Year: 2025
Title: Structural and functional characterization of human sweet taste receptor.
Authors: Zongjun Shi / Weixiu Xu / Lijie Wu / Xiaolei Yue / Shenhui Liu / Wei Ding / Jinyi Zhang / Bing Meng / Lianghao Zhao / Xiaoyan Liu / Junlin Liu / Zhi-Jie Liu / Tian Hua /
Abstract: Sweet taste perception influences dietary choices and metabolic health. The human sweet taste receptor, a class C G protein-coupled receptor (GPCR) heterodimer composed of TAS1R2-TAS1R3, senses a ...Sweet taste perception influences dietary choices and metabolic health. The human sweet taste receptor, a class C G protein-coupled receptor (GPCR) heterodimer composed of TAS1R2-TAS1R3, senses a wide range of sweet compounds - including natural sugars, artificial sweeteners and sweet proteins - impacting metabolic regulation beyond taste. However, the lack of three-dimensional structures hinders our understanding of its precise working mechanism. Here, we present cryo-EM structures of the full-length human sweet taste receptor in apo- and sucralose-bound states. These structures reveal a distinct asymmetric heterodimer architecture, with sucralose binding exclusively to the Venus flytrap domain of TAS1R2. Combining mutagenesis and molecular dynamics simulations, this work delineates the sweeteners recognition modes in TAS1R2. Structural comparisons further uncover the conformational changes upon ligand binding and unique activation mechanism. These findings illuminate the signal transduction mechanisms of chemosensory receptors in class C GPCRs and provide molecular basis for new-generation sweetener design.
History
DepositionMay 3, 2025-
Header (metadata) releaseJul 16, 2025-
Map releaseJul 16, 2025-
UpdateJul 16, 2025-
Current statusJul 16, 2025Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_64485.png

Downloads & links

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Map

FileDownload / File: emd_64485.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
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Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.96 Å/pix.
x 384 pix.
= 368.64 Å		0.96 Å/pix.
x 384 pix.
= 368.64 Å		0.96 Å/pix.
x 384 pix.
= 368.64 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.96 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.03
Minimum - Maximum-0.32810897 - 0.6697474
Average (Standard dev.)-0.00039054413 (±0.011069511)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 368.63998 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_64485_half_map_1.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_64485_half_map_2.map
Projections & Slices
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Histogram (log scale)

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Sample components

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Entire : heterodimer

EntireName: heterodimer
Components
  • Complex: heterodimer
    • Protein or peptide: Taste receptor type 1 member 2,Engineered red fluorescent protein mScarlet3
    • Protein or peptide: Taste receptor type 1 member 3,mNeonGreen

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Supramolecule #1: heterodimer

SupramoleculeName: heterodimer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Taste receptor type 1 member 2,Engineered red fluorescent protein...

MacromoleculeName: Taste receptor type 1 member 2,Engineered red fluorescent protein mScarlet3
type: protein_or_peptide / ID: 1
Details: Engineered red fluorescent protein mScarlet3: PMID: 27869816 and PDB ID: 7ZCT
Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Discosoma sp. (Sea anemone) (sea anemone)
Molecular weightTheoretical: 122.191227 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MKTIIALSYI FCLVFAGSDY KDDDDKGSAD FYLPGDYLLG GLFSLHANMK GIVHLNFLQV PMCKEYEVKV IGYNLMQAMR FAVEEINND SSLLPGVLLG YEIVDVCYIS NNVQPVLYFL AHEDNLLPIQ EDYSNYISRV VAVIGPDNSE SVMTVANFLS L FLLPQITY ...String:
MKTIIALSYI FCLVFAGSDY KDDDDKGSAD FYLPGDYLLG GLFSLHANMK GIVHLNFLQV PMCKEYEVKV IGYNLMQAMR FAVEEINND SSLLPGVLLG YEIVDVCYIS NNVQPVLYFL AHEDNLLPIQ EDYSNYISRV VAVIGPDNSE SVMTVANFLS L FLLPQITY SAISDELRDK VRFPALLRTT PSADHHIEAM VQLMLHFRWN WIIVLVSSDT YGRDNGQLLG ERVARRDICI AF QETLPTL QPNQNMTSEE RQRLVTIVDK LQQSTARVVV VFSPDLTLYH FFNEVLRQNF TGAVWIASES WAIDPVLHNL TEL RHLGTF LGITIQSVPI PGFSEFREWG PQAGPPPLSR TSQSYTCNQE CDNCLNATLS FNTILRLSGE RVVYSVYSAV YAVA HALHS LLGCDKSTCT KRVVYPWQLL EEIWKVNFTL LDHQIFFDPQ GDVALHLEIV QWQWDRSQNP FQSVASYYPL QRQLK NIQD ISWHTINNTI PMSMCSKRCQ SGQKKKPVGI HVCCFECIDC LPGTFLNHTE DEYECQACPN NEWSYQSETS CFKRQL VFL EWHEAPTIAV ALLAALGFLS TLAILVIFWR HFQTPIVRSA GGPMCFLMLT LLLVAYMVVP VYVGPPKVST CLCRQAL FP LCFTICISCI AVRSFQIVCA FKMASRFPRA YSYWVRYQGP YVSMAFITVL KMVIVVIGML ATGLSPTTRT DPDDPKIT I VSCNPNYRNS LLFNTSLDLL LSVVGFSFAY MGKELPTNYN EAKFITLSMT FYFTSSVSLC TFMSAYSGVL VTIVDLLVT VLNLLAISLG YFGPKCYMIL FYPERNTPAY FNSMIQGYTM RRDGSSGLEV LFQGPSGGDS TEAVIKEFMR FKVHMEGSMN GHEFEIEGE GEGRPYEGTQ TAKLRVTKGG PLPFSWDILS PQFMYGSRAF TKHPADIPDY WKQSFPEGFK WERVMNFEDG G AVSVAQDT SLEDGTLIYK VKLRGTNFPP DGPVMQKKTM GWEASTERLY PEDVVLKGDI KMALRLKDGG RYLADFKTTY RA KKPVQMP GAFNIDRKLD ITSHNEDYTV VEQYERSVAR H

UniProtKB: Taste receptor type 1 member 2

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Macromolecule #2: Taste receptor type 1 member 3,mNeonGreen

MacromoleculeName: Taste receptor type 1 member 3,mNeonGreen / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Branchiostoma lanceolatum (amphioxus)
Molecular weightTheoretical: 124.906602 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MKTIIALSYI FCLVFAGSDY KDDDDKGSAP LCLSQQLRMK GDYVLGGLFP LGEAEEAGLR SRTRPSSPVC TRFSSNGLLW ALAMKMAVE EINNKSDLLP GLRLGYDLFD TCSEPVVAMK PSLMFLAKAG SRDIAAYCNY TQYQPRVLAV IGPHSSELAM V TGKFFSFF ...String:
MKTIIALSYI FCLVFAGSDY KDDDDKGSAP LCLSQQLRMK GDYVLGGLFP LGEAEEAGLR SRTRPSSPVC TRFSSNGLLW ALAMKMAVE EINNKSDLLP GLRLGYDLFD TCSEPVVAMK PSLMFLAKAG SRDIAAYCNY TQYQPRVLAV IGPHSSELAM V TGKFFSFF LMPQVSYGAS MELLSARETF PSFFRTVPSD RVQLTAAAEL LQEFGWNWVA ALGSDDEYGR QGLSIFSALA AA RGICIAH EGLVPLPRAD DSRLGKVQDV LHQVNQSSVQ VVLLFASVHA AHALFNYSIS SRLSPKVWVA SEAWLTSDLV MGL PGMAQM GTVLGFLQRG AQLHEFPQYV KTHLALATDP AFCSALGERE QGLEEDVVGQ RCPQCDCITL QNVSAGLNHH QTFS VYAAV YSVAQALHNT LQCNASGCPA QDPVKPWQLL ENMYNLTFHV GGLPLRFDSS GNVDMEYDLK LWVWQGSVPR LHDVG RFNG SLRTERLKIR WHTSDNQKPV SRCSRQCQEG QVRRVKGFHS CCYDCVDCEA GSYRQNPDDI ACTFCGQDEW SPERST RCF RRRSRFLAWG EPAVLLLLLL LSLALGLVLA ALGLFVHHRD SPLVQASGGP LACFGLVCLG LVCLSVLLFP GQPSPAR CL AQQPLSHLPL TGCLSTLFLQ AAEIFVESEL PLSWADRLSG CLRGPWAWLV VLLAMLVEVA LCTWYLVAFP PEVVTDWH M LPTEALVHCR TRSWVSFGLA HATNATLAFL CFLGTFLVRS QPGCYNRARG LTFAMLAYFI TWVSFVPLLA NVQVVLRPA VQMGALLLCV LGILAAFHLP RCYLLMRQPG LNTPEFFLGG GPGDAQGQND GNTGNQGKHE GSSGLEVLFQ GPSGGVSKGE EDNMASLPA THELHIFGSI NGVDFDMVGQ GTGNPNDGYE ELNLKSTKGD LQFSPWILVP HIGYGFHQYL PYPDGMSPFQ A AMVDGSGY QVHRTMQFED GASLTVNYRY TYEGSHIKGE AQVKGTGFPA DGPVMTNSLT AADWCRSKKT YPNDKTIIST FK WSYTTGN GKRYRSTART TYTFAKPMAA NYLKNQPMYV FRKTELKHSK TELNFKEWQK AFTDVMGMDE LYKGSENLYF QSS GHHHHH HHHH

UniProtKB: Taste receptor type 1 member 3, mNeonGreen

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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: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TALOS ARCTICA
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.18 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 189062
Initial angle assignmentType: COMMON LINE
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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