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- EMDB-35771: Cryo-EM structure of the PEA-bound mTAAR9 complex -

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Basic information

Entry
Database: EMDB / ID: EMD-35771
TitleCryo-EM structure of the PEA-bound mTAAR9 complex
Map data
Sample
  • Complex: Cryo-EM structure of the PEA-bound mTAAR9 complex
    • Protein or peptide: Trace amine-associated receptor 9
  • Ligand: 2-PHENYLETHYLAMINEPhenethylamine
KeywordsPEA / mTAAR9 / MEMBRANE PROTEIN
Function / homology
Function and homology information


Amine ligand-binding receptors / trace-amine receptor activity / G alpha (s) signalling events / plasma membrane
Similarity search - Function
Trace amine associated receptor family / Serpentine type 7TM GPCR chemoreceptor Srsx / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family)
Similarity search - Domain/homology
Trace amine-associated receptor 9
Similarity search - Component
Biological speciesMus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.17 Å
AuthorsSun JP / Li Q / Yang F / Xu YF / Guo LL / Lian S / Zhang MH / Rong NK
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)2018YFC1003600 China
CitationJournal: Nature / Year: 2023
Title: Structural basis of amine odorant perception by a mammal olfactory receptor.
Authors: Lulu Guo / Jie Cheng / Shuo Lian / Qun Liu / Yan Lu / Yuan Zheng / Kongkai Zhu / Minghui Zhang / Yalei Kong / Chao Zhang / Naikang Rong / Yuming Zhuang / Guoxing Fang / Jingjing Jiang / ...Authors: Lulu Guo / Jie Cheng / Shuo Lian / Qun Liu / Yan Lu / Yuan Zheng / Kongkai Zhu / Minghui Zhang / Yalei Kong / Chao Zhang / Naikang Rong / Yuming Zhuang / Guoxing Fang / Jingjing Jiang / Tianyao Zhang / Xiang Han / Zili Liu / Ming Xia / Shangming Liu / Lei Zhang / Stephen D Liberles / Xiao Yu / Yunfei Xu / Fan Yang / Qian Li / Jin-Peng Sun /
Abstract: Odorants are detected as smell in the nasal epithelium of mammals by two G-protein-coupled receptor families, the odorant receptors and the trace amine-associated receptors (TAARs). TAARs emerged ...Odorants are detected as smell in the nasal epithelium of mammals by two G-protein-coupled receptor families, the odorant receptors and the trace amine-associated receptors (TAARs). TAARs emerged following the divergence of jawed and jawless fish, and comprise a large monophyletic family of receptors that recognize volatile amine odorants to elicit both intraspecific and interspecific innate behaviours such as attraction and aversion. Here we report cryo-electron microscopy structures of mouse TAAR9 (mTAAR9) and mTAAR9-G or mTAAR9-G trimers in complex with β-phenylethylamine, N,N-dimethylcyclohexylamine or spermidine. The mTAAR9 structures contain a deep and tight ligand-binding pocket decorated with a conserved DWY motif, which is essential for amine odorant recognition. In the mTAAR9 structure, a unique disulfide bond connecting the N terminus to ECL2 is required for agonist-induced receptor activation. We identify key structural motifs of TAAR family members for detecting monoamines and polyamines and the shared sequence of different TAAR members that are responsible for recognition of the same odour chemical. We elucidate the molecular basis of mTAAR9 coupling to G and G by structural characterization and mutational analysis. Collectively, our results provide a structural basis for odorant detection, receptor activation and G coupling of an amine olfactory receptor.
History
DepositionMar 30, 2023-
Header (metadata) releaseMay 31, 2023-
Map releaseMay 31, 2023-
UpdateJun 14, 2023-
Current statusJun 14, 2023Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_35771.png

Downloads & links

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Map

FileDownload / File: emd_35771.map.gz / Format: CCP4 / Size: 22.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.076 Å
Density
Contour LevelBy AUTHOR: 0.01
Minimum - Maximum-0.06946961 - 0.10004773
Average (Standard dev.)-0.0000024806318 (±0.0026811047)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions180180180
Spacing180180180
CellA=B=C: 193.68 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_35771_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_35771_half_map_2.map
Projections & Slices
AxesZYX

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Sample components

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Entire : Cryo-EM structure of the PEA-bound mTAAR9 complex

EntireName: Cryo-EM structure of the PEA-bound mTAAR9 complex
Components
  • Complex: Cryo-EM structure of the PEA-bound mTAAR9 complex
    • Protein or peptide: Trace amine-associated receptor 9
  • Ligand: 2-PHENYLETHYLAMINEPhenethylamine

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Supramolecule #1: Cryo-EM structure of the PEA-bound mTAAR9 complex

SupramoleculeName: Cryo-EM structure of the PEA-bound mTAAR9 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Mus musculus (house mouse)

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Macromolecule #1: Trace amine-associated receptor 9

MacromoleculeName: Trace amine-associated receptor 9 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 38.928238 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MTSDFSPEPP MELCYENVNG SCIKSSYAPW PRAILYGVLG LGALLAVFGN LLVIIAILHF KQLHTPTNFL VASLACADFL VGVTVMPFS TVRSVESCWY FGESYCKFHT CFDTSFCFAS LFHLCCISID RYIAVTDPLT YPTKFTVSVS GLCIALSWFF S VTYSFSIF ...String:
MTSDFSPEPP MELCYENVNG SCIKSSYAPW PRAILYGVLG LGALLAVFGN LLVIIAILHF KQLHTPTNFL VASLACADFL VGVTVMPFS TVRSVESCWY FGESYCKFHT CFDTSFCFAS LFHLCCISID RYIAVTDPLT YPTKFTVSVS GLCIALSWFF S VTYSFSIF YTGANEEGIE ELVVALTCVG GCQAPLNQNW VLLCFLLFFL PTVVMVFLYG RIFLVAKYQA RKIEGTANQA QA SSESYKE RVAKRERKAA KTLGIAMAAF LVSWLPYIID AVIDAYMNFI TPAYVYEILV WCVYYNSAMN PLIYAFFYPW FRK AIKLIV SGKVFRADSS TTNLFSEEAG AG

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Macromolecule #2: 2-PHENYLETHYLAMINE

MacromoleculeName: 2-PHENYLETHYLAMINE / type: ligand / ID: 2 / Number of copies: 1 / Formula: PEA
Molecular weightTheoretical: 122.188 Da
Chemical component information

ChemComp-PEA:
2-PHENYLETHYLAMINE / alkaloid*YM / Phenethylamine

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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
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: DIFFRACTION / 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: 1.875 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: OTHER
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.17 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 463012

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