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- EMDB-65621: The structure of odorant-bound mouse class II odorant receptor-mi... -

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Basic information

Entry
Database: EMDB / ID: EMD-65621
TitleThe structure of odorant-bound mouse class II odorant receptor-miniGs complex
Map dataComposite map
Sample
  • Complex: Complex of Odorant-bound Olfr412 and heterotrimeric G protein
    • Complex: mini G
      • Protein or peptide: Guanine nucleotide-binding protein G(s) subunit alpha
    • Complex: G protein
      • 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
    • Complex: nanobody
      • Protein or peptide: Nanobody 35
    • Complex: receptor
      • Protein or peptide: Olfactory receptor
  • Ligand: Methyl cinnamate
KeywordsOdorant receptor / MEMBRANE PROTEIN / MEMBRANE PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


Olfactory Signaling Pathway / olfactory receptor activity / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor ...Olfactory Signaling Pathway / olfactory receptor activity / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / sensory perception of smell / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G beta:gamma signalling through BTK / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G alpha (12/13) signalling events / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / extracellular vesicle / sensory perception of taste / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / retina development in camera-type eye / GTPase binding / fibroblast proliferation / Ca2+ pathway / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / 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 / GTP binding / protein-containing complex binding / signal transduction / extracellular exosome / membrane / metal ion binding / identical protein binding / plasma membrane / cytoplasm / cytosol
Similarity search - Function
Olfactory receptor / Olfactory receptor / G-protein alpha subunit, group S / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / G-protein, gamma subunit / G-protein gamma subunit domain profile. ...Olfactory receptor / Olfactory receptor / G-protein alpha subunit, group S / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / 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 / G protein beta WD-40 repeat protein / 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. / 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 / Olfactory receptor
Similarity search - Component
Biological speciesHomo sapiens (human) / Lama glama (llama) / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsChoi CW / Gil MS / Choi H-J
Funding support Korea, Republic Of, 2 items
OrganizationGrant numberCountry
Samsung Science and Technology Foundation Korea, Republic Of
National Research Foundation (NRF, Korea) Korea, Republic Of
CitationJournal: Sci Adv / Year: 2026
Title: Structural basis of odorant recognition by a mammalian class II odorant receptor.
Authors: Minsu Gil / Chulwon Choi / Minseok Kim / Minsik Bae / Hajin Lee / Intae Choi / Wonpil Im / Hee-Jung Choi /
Abstract: Mammalian odorant receptors (ORs) sense diverse environmental chemicals, yet structural insights into odorant recognition by mammalian class II ORs remain limited. Here, we present the cryo-EM ...Mammalian odorant receptors (ORs) sense diverse environmental chemicals, yet structural insights into odorant recognition by mammalian class II ORs remain limited. Here, we present the cryo-EM structure of a native mammalian class II OR, mouse Olfr412, a human OR1D2 ortholog, bound to the odorant methyl--cinnamate and the G protein. The odorant-binding pocket of Olfr412 is located deeper within the transmembrane domain than that of the class I OR OR51E2 and is largely composed of poorly conserved hydrophobic residues, providing a structural basis for broad odorant recognition in class II ORs. Structural and molecular dynamics analyses suggest that the conserved Y plays a key role in odorant recognition and activation, functionally paralleling R in class I ORs and is further stabilized by intramolecular interaction with the conserved ECL2 residue E. Together, our findings uncover structural mechanisms underlying odorant recognition and activation in class II ORs.
History
DepositionJul 30, 2025-
Header (metadata) releaseMar 4, 2026-
Map releaseMar 4, 2026-
UpdateMay 6, 2026-
Current statusMay 6, 2026Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_65621.png

Downloads & links

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Map

FileDownload / File: emd_65621.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationComposite map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 400 pix.
= 331.2 Å		0.83 Å/pix.
x 400 pix.
= 331.2 Å		0.83 Å/pix.
x 400 pix.
= 331.2 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.828 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.12
Minimum - Maximum-0.5686767 - 1.1344534
Average (Standard dev.)0.0026636382 (±0.015290332)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 331.2 Å
α=β=γ: 90.0 °

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Supplemental data

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Sample components

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Entire : Complex of Odorant-bound Olfr412 and heterotrimeric G protein

EntireName: Complex of Odorant-bound Olfr412 and heterotrimeric G protein
Components
  • Complex: Complex of Odorant-bound Olfr412 and heterotrimeric G protein
    • Complex: mini G
      • Protein or peptide: Guanine nucleotide-binding protein G(s) subunit alpha
    • Complex: G protein
      • 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
    • Complex: nanobody
      • Protein or peptide: Nanobody 35
    • Complex: receptor
      • Protein or peptide: Olfactory receptor
  • Ligand: Methyl cinnamate

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Supramolecule #1: Complex of Odorant-bound Olfr412 and heterotrimeric G protein

SupramoleculeName: Complex of Odorant-bound Olfr412 and heterotrimeric G protein
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5

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Supramolecule #2: mini G

SupramoleculeName: mini G / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #3: G protein

SupramoleculeName: G protein / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #4: nanobody

SupramoleculeName: nanobody / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #4
Source (natural)Organism: Lama glama (llama)

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Supramolecule #5: receptor

SupramoleculeName: receptor / type: complex / ID: 5 / Parent: 1 / Macromolecule list: #5
Source (natural)Organism: Mus musculus (house mouse)

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Macromolecule #1: Guanine nucleotide-binding protein G(s) subunit alpha

MacromoleculeName: Guanine nucleotide-binding protein G(s) subunit alpha / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 29.051812 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: GSNSKTEDQR NEEKAQREAN KKIEKQLQKD KQVYRATHRL LLLGADNSGK STIVKQMRIL HGGSGGSGGT SGIFETKFQV DKVNFHMFD VGGQRDERRK WIQCFNDVTA IIFVVDSSDY NRLQEALNLF KSIWNNRWLR TISVILFLNK QDLLAEKVLA G KSKIEDYF ...String:
GSNSKTEDQR NEEKAQREAN KKIEKQLQKD KQVYRATHRL LLLGADNSGK STIVKQMRIL HGGSGGSGGT SGIFETKFQV DKVNFHMFD VGGQRDERRK WIQCFNDVTA IIFVVDSSDY NRLQEALNLF KSIWNNRWLR TISVILFLNK QDLLAEKVLA G KSKIEDYF PEFARYTTPE DATPEPGEDP RVTRAKYFIR DEFLRISTAS GDGRHYCYPH FTCAVDTENA RRIFNDCRDI IQ RMHLRQY ELL

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

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Macromolecule #2: 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: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 39.418086 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MHHHHHHLEV LFQGPGSSGS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR ...String:
MHHHHHHLEV LFQGPGSSGS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR FLDDNQIVTS SGDTTCALWD IETGQQTTTF TGHTGDVMSL SLAPDTRLFV SGACDASAKL WDVREGMCRQ TF TGHESDI NAICFFPNGN AFATGSDDAT CRLFDLRADQ ELMTYSHDNI ICGITSVSFS KSGRLLLAGY DDFNCNVWDA LKA DRAGVL AGHDNRVSCL GVTDDGMAVA TGSWDSFLKI WN

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

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Macromolecule #3: 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: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 7.861143 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
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 #4: Nanobody 35

MacromoleculeName: Nanobody 35 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Lama glama (llama)
Molecular weightTheoretical: 14.273889 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
VQLQESGGGL VQPGGSLRLS CAASGFTFSN YKMNWVRQAP GKGLEWVSDI SQSGASISYT GSVKGRFTIS RDNAKNTLYL QMNSLKPED TAVYYCARCP APFTRDCFDV TSTTYAYRGQ GTQVTVHHHH H

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Macromolecule #5: Olfactory receptor

MacromoleculeName: Olfactory receptor / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 35.201219 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MDGGNQSGDS EFLLLGLSEV PEHQRILFWT FLSMYLVTVV GNVLIILAIG SDSHLHTPMY FFLANLSFTD LFFVTNTIPK MLVSLQSQN KAISYPGCLT QLFFLVSLVA LDNLILAVMA YDRYVAICHP LHYTTAMSPK LCILLLILCW ALSILYGLIH T LLMTRVTF ...String:
MDGGNQSGDS EFLLLGLSEV PEHQRILFWT FLSMYLVTVV GNVLIILAIG SDSHLHTPMY FFLANLSFTD LFFVTNTIPK MLVSLQSQN KAISYPGCLT QLFFLVSLVA LDNLILAVMA YDRYVAICHP LHYTTAMSPK LCILLLILCW ALSILYGLIH T LLMTRVTF CGSRKIHYIF CEMYVLLRLA CSNTHINHMM LIATGCFVFL VPFGFMIMSY ICIVRAILKI PSASNKYKAF ST CASHLAV VALFYGTLCM VYLKPVHTYS MKDSVATVMY AVVTPMMNPF IYSLRNKDMH GALGRLLRKP LQKLT

UniProtKB: Olfactory receptor

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Macromolecule #6: Methyl cinnamate

MacromoleculeName: Methyl cinnamate / type: ligand / ID: 6 / Number of copies: 1 / Formula: A1MBB
Molecular weightTheoretical: 162.185 Da

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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: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 62.2 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 1.7 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: NONE
Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 94056
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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