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Structure paper

TitleThe structure of human sweetness.
Journal, issue, pagesCell, Year 2025
Publish dateMay 2, 2025
AuthorsZhang Juen / Zhengyuan Lu / Ruihuan Yu / Andrew N Chang / Brian Wang / Anthony W P Fitzpatrick / Charles S Zuker /
PubMed AbstractIn 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.
External linksCell / PubMed:40339580
MethodsEM (single particle)
Resolution2.8 - 4.3 Å
Structure data

EMDB-49605: Local refinement map of the human sweet taste receptor Venus Fly Trap domains (VFT) and upper-half of the Cysteine-Rich domains (CR) from the combined datasets
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-49606: Local refinement map of the human sweet taste receptor lower-half of the Cysteine-Rich domains (CR) and transmembrane domains (TMD) from the combined datasets
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-49607: Consensus map of the human sweet taste receptor composed of TAS1R2 and TAS1R3 GPCRs from the combined datasets
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-49608, PDB-9nor:
Human sweet taste receptor composed of TAS1R2 and TAS1R3 GPCRs from the combined datasets
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-49609: Local refinement map of the human sweet taste receptor Venus Fly Trap domains (VFT) and upper-half of the cysteine-rich domains (CR) from the PEG400 dataset
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-49610: Local refinement map of the human sweet taste receptor lower-half of the Cysteine-Rich domains (CR) and transmembrane domains (TMD) from the PEG400 dataset
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-49611: Consensus map of the human sweet taste receptor (TAS1R2 + TAS1R3) from the PEG400 dataset
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-49612, PDB-9nos:
Human sweet taste receptor (TAS1R2 + TAS1R3) from the PEG400 dataset
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-49613: Local refinement map of the human sweet taste receptor Venus Fly Trap domains (VFT) and upper-half of the Cysteine-Rich domains (CR) from the sucralose dataset
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-49614: Local refinement map of the human sweet taste receptor lower-half of the Cysteine-Rich domains (CR) and transmembrane domains (TMD) from the sucralose dataset
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-49615: Consensus map of the human sweet taste receptor (TAS1R2 + TAS1R3) from the sucralose dataset
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-49616, PDB-9not:
Human sweet taste receptor (TAS1R2 + TAS1R3) from the sucralose dataset
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-49617, PDB-9nou:
Human sweet taste receptor (TAS1R2 + TAS1R3) VFT domains from the combined datasets
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-49618, PDB-9nov:
Human sweet taste receptor (TAS1R2 + TAS1R3) VFT domains bound to sucralose
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-49619, PDB-9now:
Human sweet taste receptor (TAS1R2 + TAS1R3) VFT domains bound to aspartame
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-49620, PDB-9nox:
Transmembrane domains of the human TAS1R2 sweet receptor subunit in complex with miniGs/gust25
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-49621, PDB-9noy:
Human TAS1R2 transmembrane domains from the TAS1R2-TM-G protein complex
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-70072, PDB-9o38:
Transmembrane domains of the human sweet receptor (TAS1R2 + TAS1R3) from Class 3 particles (rigidly fitted from PDB:9NOX and 9NOR)
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-70073: Consensus map of the Human sweet taste receptor (TAS1R2 + TAS1R3) from the aspartame dataset
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

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

Source
  • homo sapiens (human)
  • lama glama (llama)
KeywordsMEMBRANE PROTEIN / Sweet / taste / receptor / GPCR / TAS1R2 / TAS1R3 / T1R2 / T1R3 / human / HYDROLASE/IMMUNE SYSTEM / HYDROLASE-IMMUNE SYSTEM complex

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