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- EMDB-28896: Human olfactory receptor OR51E2 bound to propionate in complex wi... -

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Entry
Database: EMDB / ID: EMD-28896
TitleHuman olfactory receptor OR51E2 bound to propionate in complex with miniGs399
Map dataSharpened map from cryoSPARC
Sample
  • Complex: OR51E2-Gs complex
    • Protein or peptide: Olfactory receptor 51E2
    • Protein or peptide: Nanobody 35
    • Protein or peptide: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
  • Ligand: PROPANOIC ACID
KeywordsHuman olfactory receptor / G protein-coupled receptor / odorant-binding / sensory transduction / MEMBRANE PROTEIN
Function / homology
Function and homology information


melanocyte proliferation / positive regulation of renin secretion into blood stream / Expression and translocation of olfactory receptors / olfactory receptor activity / intracellular organelle / melanocyte differentiation / positive regulation of blood pressure / cellular response to fatty acid / nuclear steroid receptor activity / steroid hormone receptor signaling pathway ...melanocyte proliferation / positive regulation of renin secretion into blood stream / Expression and translocation of olfactory receptors / olfactory receptor activity / intracellular organelle / melanocyte differentiation / positive regulation of blood pressure / cellular response to fatty acid / nuclear steroid receptor activity / steroid hormone receptor signaling pathway / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / regulation of insulin secretion / cellular response to glucagon stimulus / adenylate cyclase activator activity / trans-Golgi network membrane / negative regulation of inflammatory response to antigenic stimulus / G protein-coupled receptor activity / bone development / G-protein beta/gamma-subunit complex binding / platelet aggregation / Olfactory Signaling Pathway / cognition / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / sensory perception of smell / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / cell migration / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / signaling receptor activity / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of cold-induced thermogenesis / G protein activity / GTPase binding / Ca2+ pathway / retina development in camera-type eye / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / early endosome membrane / fibroblast proliferation / G alpha (i) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome / metal ion binding / membrane / plasma membrane / cytosol
Similarity search - Function
Olfactory receptor / : / Olfactory receptor / G-protein alpha subunit, group S / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / G-protein, gamma subunit ...Olfactory receptor / : / Olfactory receptor / G-protein alpha subunit, group S / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / WD domain, G-beta repeat / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(s) subunit alpha isoforms short / Olfactory receptor 51E2
Similarity search - Component
Biological speciesHomo sapiens (human) / Lama glama (llama)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsBillesboelle CB / Manglik A
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute on Deafness and Other Communication Disorders (NIH/NIDCD)R01DC020353 United States
CitationJournal: Nature / Year: 2023
Title: Structural basis of odorant recognition by a human odorant receptor.
Authors: Christian B Billesbølle / Claire A de March / Wijnand J C van der Velden / Ning Ma / Jeevan Tewari / Claudia Llinas Del Torrent / Linus Li / Bryan Faust / Nagarajan Vaidehi / Hiroaki ...Authors: Christian B Billesbølle / Claire A de March / Wijnand J C van der Velden / Ning Ma / Jeevan Tewari / Claudia Llinas Del Torrent / Linus Li / Bryan Faust / Nagarajan Vaidehi / Hiroaki Matsunami / Aashish Manglik /
Abstract: Our sense of smell enables us to navigate a vast space of chemically diverse odour molecules. This task is accomplished by the combinatorial activation of approximately 400 odorant G protein-coupled ...Our sense of smell enables us to navigate a vast space of chemically diverse odour molecules. This task is accomplished by the combinatorial activation of approximately 400 odorant G protein-coupled receptors encoded in the human genome. How odorants are recognized by odorant receptors remains unclear. Here we provide mechanistic insight into how an odorant binds to a human odorant receptor. Using cryo-electron microscopy, we determined the structure of the active human odorant receptor OR51E2 bound to the fatty acid propionate. Propionate is bound within an occluded pocket in OR51E2 and makes specific contacts critical to receptor activation. Mutation of the odorant-binding pocket in OR51E2 alters the recognition spectrum for fatty acids of varying chain length, suggesting that odorant selectivity is controlled by tight packing interactions between an odorant and an odorant receptor. Molecular dynamics simulations demonstrate that propionate-induced conformational changes in extracellular loop 3 activate OR51E2. Together, our studies provide a high-resolution view of chemical recognition of an odorant by a vertebrate odorant receptor, providing insight into how this large family of G protein-coupled receptors enables our olfactory sense.
History
DepositionNov 18, 2022-
Header (metadata) releaseMar 22, 2023-
Map releaseMar 22, 2023-
UpdateMay 28, 2025-
Current statusMay 28, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_28896.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationSharpened map from cryoSPARC
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.81 Å/pix.
x 288 pix.
= 233.28 Å
0.81 Å/pix.
x 288 pix.
= 233.28 Å
0.81 Å/pix.
x 288 pix.
= 233.28 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.81 Å
Density
Contour LevelBy AUTHOR: 0.54
Minimum - Maximum-3.1718035 - 4.9646034
Average (Standard dev.)0.014998866 (±0.11113737)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions288288288
Spacing288288288
CellA=B=C: 233.28 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_28896_msk_1.map
Projections & Slices
AxesZYX

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Additional map: Unsharpened map from cryoSPARC

Fileemd_28896_additional_1.map
AnnotationUnsharpened map from cryoSPARC
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

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Half map: Half map A from cryoSPARC

Fileemd_28896_half_map_1.map
AnnotationHalf map A from cryoSPARC
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: Half map B from cryoSPARC

Fileemd_28896_half_map_2.map
AnnotationHalf map B from cryoSPARC
Projections & Slices
AxesZYX

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Sample components

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Entire : OR51E2-Gs complex

EntireName: OR51E2-Gs complex
Components
  • Complex: OR51E2-Gs complex
    • Protein or peptide: Olfactory receptor 51E2
    • Protein or peptide: Nanobody 35
    • Protein or peptide: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
    • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
  • Ligand: PROPANOIC ACID

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Supramolecule #1: OR51E2-Gs complex

SupramoleculeName: OR51E2-Gs complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 100 KDa

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Macromolecule #1: Olfactory receptor 51E2

MacromoleculeName: Olfactory receptor 51E2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 36.651543 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DYKDDDDASI DSSCNFTHAT FVLIGIPGLE KAHFWVGFPL LSMYVVAMFG NCIVVFIVRT ERSLHAPMYL FLCMLAAIDL ALSTSTMPK ILALFWFDSR EISFEACLTQ MFFIHALSAI ESTILLAMAF DRYVAICHPL RHAAVLNNTV TAQIGIVAVV R GSLFFFPL ...String:
DYKDDDDASI DSSCNFTHAT FVLIGIPGLE KAHFWVGFPL LSMYVVAMFG NCIVVFIVRT ERSLHAPMYL FLCMLAAIDL ALSTSTMPK ILALFWFDSR EISFEACLTQ MFFIHALSAI ESTILLAMAF DRYVAICHPL RHAAVLNNTV TAQIGIVAVV R GSLFFFPL PLLIKRLAFC HSNVLSHSYC VHQDVMKLAY ADTLPNVVYG LTAILLVMGV DVMFISLSYF LIIRTVLQLP SK SERAKAF GTCVSHIGVV LAFYVPLIGL SVVHRFGNSL HPIVRVVMGD IYLLLPPVIN PIIYGAKTKQ IRTRVLAMFK ISC DKDLQA VGGK

UniProtKB: Olfactory receptor 51E2

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Macromolecule #2: Nanobody 35

MacromoleculeName: Nanobody 35 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Lama glama (llama)
Molecular weightTheoretical: 15.931698 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSSL EVLFQGPGHH HHHHHH

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Macromolecule #3: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short

MacromoleculeName: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 30.137025 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: GGSLEVLFQG PSGNSKTEDQ RNEEKAQREA NKKIEKQLQK DKQVYRATHR LLLLGADNSG KSTIVKQMRI LHGGSGGSGG TSGIFETKF QVDKVNFHMF DVGGQRDERR KWIQCFNDVT AIIFVVDSSD YNRLQEALNL FKSIWNNRWL RTISVILFLN K QDLLAEKV ...String:
GGSLEVLFQG PSGNSKTEDQ RNEEKAQREA NKKIEKQLQK DKQVYRATHR LLLLGADNSG KSTIVKQMRI LHGGSGGSGG TSGIFETKF QVDKVNFHMF DVGGQRDERR KWIQCFNDVT AIIFVVDSSD YNRLQEALNL FKSIWNNRWL RTISVILFLN K QDLLAEKV LAGKSKIEDY FPEFARYTTP EDATPEPGED PRVTRAKYFI RDEFLRISTA SGDGRHYCYP HFTCAVDTEN AR RIFNDCR DIIQRMHLRQ YELL

UniProtKB: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short

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Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

MacromoleculeName: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 40.786566 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: MHHHHHHLEV LFQGPEDQVD PRLIDGKGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIY AMHWGTDSRL LVSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR E GNVRVSRE ...String:
MHHHHHHLEV LFQGPEDQVD PRLIDGKGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIY AMHWGTDSRL LVSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR E GNVRVSRE LAGHTGYLSC CRFLDDNQIV TSSGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KL WDVREGM CRQTFTGHES DINAICFFPN GNAFATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYD DFNCNV WDALKADRAG VLAGHDNRVS CLGVTDDGMA VATGSWDSFL KIWN

UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

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Macromolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2

MacromoleculeName: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 7.861143 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString:
MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L

UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2

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Macromolecule #6: PROPANOIC ACID

MacromoleculeName: PROPANOIC ACID / type: ligand / ID: 6 / Number of copies: 1 / Formula: PPI
Molecular weightTheoretical: 74.079 Da
Chemical component information

ChemComp-PPI:
PROPANOIC ACID

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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
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 105000
Sample stageCooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 204438
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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