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- EMDB-23374: The structure of the insect olfactory receptor OR5 from Machilis ... -

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Basic information

Entry
Database: EMDB / ID: EMD-23374
TitleThe structure of the insect olfactory receptor OR5 from Machilis hrabei in complex with eugenol
Map dataolfactory receptor OR5 from Machilis hrabei in complex with eugenol
Sample
  • Complex: Homotetrameric olfactory receptor MhOR5 in complex with eugenol
    • Protein or peptide: MhOR5
  • Ligand: 2-methoxy-4-(prop-2-en-1-yl)phenol
Biological speciesMachilis hrabei (insect)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.9 Å
Authorsdel Marmol J / Ruta V
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID) United States
CitationJournal: Nature / Year: 2021
Title: The structural basis of odorant recognition in insect olfactory receptors.
Authors: Josefina Del Mármol / Mackenzie A Yedlin / Vanessa Ruta /
Abstract: Olfactory systems must detect and discriminate amongst an enormous variety of odorants. To contend with this challenge, diverse species have converged on a common strategy in which odorant identity ...Olfactory systems must detect and discriminate amongst an enormous variety of odorants. To contend with this challenge, diverse species have converged on a common strategy in which odorant identity is encoded through the combinatorial activation of large families of olfactory receptors, thus allowing a finite number of receptors to detect a vast chemical world. Here we offer structural and mechanistic insight into how an individual olfactory receptor can flexibly recognize diverse odorants. We show that the olfactory receptor MhOR5 from the jumping bristletail Machilis hrabei assembles as a homotetrameric odorant-gated ion channel with broad chemical tuning. Using cryo-electron microscopy, we elucidated the structure of MhOR5 in multiple gating states, alone and in complex with two of its agonists-the odorant eugenol and the insect repellent DEET. Both ligands are recognized through distributed hydrophobic interactions within the same geometrically simple binding pocket located in the transmembrane region of each subunit, suggesting a structural logic for the promiscuous chemical sensitivity of this receptor. Mutation of individual residues lining the binding pocket predictably altered the sensitivity of MhOR5 to eugenol and DEET and broadly reconfigured the receptor's tuning. Together, our data support a model in which diverse odorants share the same structural determinants for binding, shedding light on the molecular recognition mechanisms that ultimately endow the olfactory system with its immense discriminatory capacity.
History
DepositionJan 27, 2021-
Header (metadata) releaseAug 11, 2021-
Map releaseAug 11, 2021-
UpdateFeb 23, 2022-
Current statusFeb 23, 2022Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.997
  • Imaged by UCSF Chimera
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  • Surface view colored by cylindrical radius
  • Surface level: 0.997
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-7lid
  • Surface level: 0.997
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_23374.png

Downloads & links

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Map

FileDownload / File: emd_23374.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationolfactory receptor OR5 from Machilis hrabei in complex with eugenol
Voxel sizeX=Y=Z: 1.03 Å
Density
Contour LevelBy AUTHOR: 0.997 / Movie #1: 0.997
Minimum - Maximum-3.379724 - 4.192539
Average (Standard dev.)0.0024078365 (±0.105375975)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 309.0 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.031.031.03
M x/y/z300300300
origin x/y/z0.0000.0000.000
length x/y/z309.000309.000309.000
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ400400400
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS300300300
D min/max/mean-3.3804.1930.002

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Supplemental data

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Sample components

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Entire : Homotetrameric olfactory receptor MhOR5 in complex with eugenol

EntireName: Homotetrameric olfactory receptor MhOR5 in complex with eugenol
Components
  • Complex: Homotetrameric olfactory receptor MhOR5 in complex with eugenol
    • Protein or peptide: MhOR5
  • Ligand: 2-methoxy-4-(prop-2-en-1-yl)phenol

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Supramolecule #1: Homotetrameric olfactory receptor MhOR5 in complex with eugenol

SupramoleculeName: Homotetrameric olfactory receptor MhOR5 in complex with eugenol
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Machilis hrabei (insect)
Recombinant expressionOrganism: Homo sapiens (human)

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Macromolecule #1: MhOR5

MacromoleculeName: MhOR5 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Machilis hrabei (insect)
Molecular weightTheoretical: 53.736695 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: GPGRAKIDVD SVDHTDDYIH LRKWIKRIGI ILRISGHWPF RLPHEKRNQH KSKFRQVYSC LVITLGFITC SCYCIGLCLS ESIAQALNN ITVTSYFLQS CVCYVSFIIN SRKLETLFNY LFENEVVGCP RGYKMSSIKT TLFRCKFVAF SLGILSFFGW L MWTLLPLA ...String:
GPGRAKIDVD SVDHTDDYIH LRKWIKRIGI ILRISGHWPF RLPHEKRNQH KSKFRQVYSC LVITLGFITC SCYCIGLCLS ESIAQALNN ITVTSYFLQS CVCYVSFIIN SRKLETLFNY LFENEVVGCP RGYKMSSIKT TLFRCKFVAF SLGILSFFGW L MWTLLPLA VLVVDSGATG GGNQTSLRFV EAWYPFDTTT SPMNEVIAIY EAVAMIFLIT APMSSDIMFC VLMIFIVEHL KC LGMAIEC TLKGISTNQH QNIGFDDSVS DVNVQRRIVI GKESPIQSIH VPIKECSRQS SDAVFREKRH GTHHQIIRSH NYT DATSLC NIVDSHVKIY RTMEIVQSVY SSYFATLFFT SCLAVCALAY FLAATSTSFT RVPGMVLYLM YIFLRIFLLC LLAT EVAEQ GLNLCHAGYS SKLVLASDHV RSTIQAIATR AQIPLSITGA RFFTVNLSFL ASMAGVMLTY FIVLLQVNAK PKP

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Macromolecule #2: 2-methoxy-4-(prop-2-en-1-yl)phenol

MacromoleculeName: 2-methoxy-4-(prop-2-en-1-yl)phenol / type: ligand / ID: 2 / Number of copies: 4 / Formula: EOL
Molecular weightTheoretical: 164.201 Da
Chemical component information

ChemComp-EOL:
2-methoxy-4-(prop-2-en-1-yl)phenol / Eugenol

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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 / Component - Concentration: 0.5 mM / Component - Name: eugenol
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: BRIGHT FIELDBright-field microscopy
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 1.51 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: OTHER / Details: initial model
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 54900
FSC plot (resolution estimation)

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