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- EMDB-35533: Cryo-EM structure of the eicosapentaenoic acid bound GPR120-Gi co... -

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Basic information

Entry
Database: EMDB / ID: EMD-35533
TitleCryo-EM structure of the eicosapentaenoic acid bound GPR120-Gi complex(consensus map)
Map data
Sample
  • Complex: Cryo-EM structure of the eicosapentaenoic acid bound GPR120-Gi complex
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.0 Å
AuthorsMao C / Xiao P / Tao X / Qin J / He Q / Zhang C / Yu X / Zhang Y / Sun J
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Science / Year: 2023
Title: Unsaturated bond recognition leads to biased signal in a fatty acid receptor.
Authors: Chunyou Mao / Peng Xiao / Xiao-Na Tao / Jiao Qin / Qing-Tao He / Chao Zhang / Sheng-Chao Guo / Ya-Qin Du / Li-Nan Chen / Dan-Dan Shen / Zhi-Shuai Yang / Han-Qiong Zhang / Shen-Ming Huang / ...Authors: Chunyou Mao / Peng Xiao / Xiao-Na Tao / Jiao Qin / Qing-Tao He / Chao Zhang / Sheng-Chao Guo / Ya-Qin Du / Li-Nan Chen / Dan-Dan Shen / Zhi-Shuai Yang / Han-Qiong Zhang / Shen-Ming Huang / Yong-Hao He / Jie Cheng / Ya-Ni Zhong / Pan Shang / Jun Chen / Dao-Lai Zhang / Qian-Lang Wang / Mei-Xia Liu / Guo-Yu Li / Yongyuan Guo / H Eric Xu / Chuanxin Wang / Cheng Zhang / Shiqing Feng / Xiao Yu / Yan Zhang / Jin-Peng Sun /
Abstract: Individual free fatty acids (FAs) play important roles in metabolic homeostasis, many through engagement with more than 40G protein-coupled receptors. Searching for receptors to sense beneficial ...Individual free fatty acids (FAs) play important roles in metabolic homeostasis, many through engagement with more than 40G protein-coupled receptors. Searching for receptors to sense beneficial omega-3 FAs of fish oil enabled the identification of GPR120, which is involved in a spectrum of metabolic diseases. Here, we report six cryo-electron microscopy structures of GPR120 in complex with FA hormones or TUG891 and G or G trimers. Aromatic residues inside the GPR120 ligand pocket were responsible for recognizing different double-bond positions of these FAs and connect ligand recognition to distinct effector coupling. We also investigated synthetic ligand selectivity and the structural basis of missense single-nucleotide polymorphisms. We reveal how GPR120 differentiates rigid double bonds and flexible single bonds. The knowledge gleaned here may facilitate rational drug design targeting to GPR120.
History
DepositionMar 3, 2023-
Header (metadata) releaseMar 22, 2023-
Map releaseMar 22, 2023-
UpdateApr 19, 2023-
Current statusApr 19, 2023Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_35533.png

Downloads & links

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Map

FileDownload / File: emd_35533.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.01 Å/pix.
x 192 pix.
= 194.688 Å		1.01 Å/pix.
x 192 pix.
= 194.688 Å		1.01 Å/pix.
x 192 pix.
= 194.688 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.014 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.1
Minimum - Maximum-0.34106755 - 0.7444518
Average (Standard dev.)0.00077711325 (±0.023255406)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions192192192
Spacing192192192
CellA=B=C: 194.68802 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_35533_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_35533_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 : Cryo-EM structure of the eicosapentaenoic acid bound GPR120-Gi complex

EntireName: Cryo-EM structure of the eicosapentaenoic acid bound GPR120-Gi complex
Components
  • Complex: Cryo-EM structure of the eicosapentaenoic acid bound GPR120-Gi complex

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Supramolecule #1: Cryo-EM structure of the eicosapentaenoic acid bound GPR120-Gi complex

SupramoleculeName: Cryo-EM structure of the eicosapentaenoic acid bound GPR120-Gi complex
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

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 62.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 2.5 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 880881
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: MAXIMUM LIKELIHOOD

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