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- EMDB-43656: CryoEM structure of Gi-coupled TAS2R14 with cholesterol and an in... -

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Basic information

Entry
Database: EMDB / ID: EMD-43656
TitleCryoEM structure of Gi-coupled TAS2R14 with cholesterol and an intracellular tastant (Locally refined map)
Map data
Sample
  • Complex: Ternary complex of TAS2R14 with Gi heterotrimer
KeywordsGPCR / Complex / SIGNALING PROTEIN / Taste receptor
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.9 Å
AuthorsKim Y / Gumpper RH / Roth BL
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)DK116195 United States
CitationJournal: Nature / Year: 2024
Title: Bitter taste receptor activation by cholesterol and an intracellular tastant.
Authors: Yoojoong Kim / Ryan H Gumpper / Yongfeng Liu / D Dewran Kocak / Yan Xiong / Can Cao / Zhijie Deng / Brian E Krumm / Manish K Jain / Shicheng Zhang / Jian Jin / Bryan L Roth /
Abstract: Bitter taste sensing is mediated by type 2 taste receptors (TAS2Rs (also known as T2Rs)), which represent a distinct class of G-protein-coupled receptors. Among the 26 members of the TAS2Rs, TAS2R14 ...Bitter taste sensing is mediated by type 2 taste receptors (TAS2Rs (also known as T2Rs)), which represent a distinct class of G-protein-coupled receptors. Among the 26 members of the TAS2Rs, TAS2R14 is highly expressed in extraoral tissues and mediates the responses to more than 100 structurally diverse tastants, although the molecular mechanisms for recognizing diverse chemicals and initiating cellular signalling are still poorly understood. Here we report two cryo-electron microscopy structures for TAS2R14 complexed with G (also known as gustducin) and G. Both structures have an orthosteric binding pocket occupied by endogenous cholesterol as well as an intracellular allosteric site bound by the bitter tastant cmpd28.1, including a direct interaction with the α5 helix of G and G. Computational and biochemical studies validate both ligand interactions. Our functional analysis identified cholesterol as an orthosteric agonist and the bitter tastant cmpd28.1 as a positive allosteric modulator with direct agonist activity at TAS2R14. Moreover, the orthosteric pocket is connected to the allosteric site via an elongated cavity, which has a hydrophobic core rich in aromatic residues. Our findings provide insights into the ligand recognition of bitter taste receptors and suggest activities of TAS2R14 beyond bitter taste perception via intracellular allosteric tastants.
History
DepositionFeb 8, 2024-
Header (metadata) releaseApr 3, 2024-
Map releaseApr 3, 2024-
UpdateApr 24, 2024-
Current statusApr 24, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_43656.png

Downloads & links

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Map

FileDownload / File: emd_43656.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
0.88 Å/pix.
x 300 pix.
= 262.8 Å		0.88 Å/pix.
x 300 pix.
= 262.8 Å		0.88 Å/pix.
x 300 pix.
= 262.8 Å

Surface

Projections

Slices (1/3)

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.876 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.72
Minimum - Maximum-5.5064735 - 7.32012
Average (Standard dev.)-0.0026596256 (±0.0857663)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 262.8 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_43656_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_43656_half_map_2.map
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Sample components

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Entire : Ternary complex of TAS2R14 with Gi heterotrimer

EntireName: Ternary complex of TAS2R14 with Gi heterotrimer
Components
  • Complex: Ternary complex of TAS2R14 with Gi heterotrimer

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Supramolecule #1: Ternary complex of TAS2R14 with Gi heterotrimer

SupramoleculeName: Ternary complex of TAS2R14 with Gi heterotrimer / type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Homo sapiens (human)

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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-PROPANE / Chamber humidity: 100 %

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Electron microscopy

MicroscopeFEI TALOS ARCTICA
Electron beamAcceleration voltage: 200 kV / Electron source: OTHER
Electron opticsIllumination mode: SPOT SCAN / Imaging mode: OTHER / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 2793137
Startup modelType of model: NONE
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.2) / Number images used: 787890

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