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Yorodumi- EMDB-42791: Consensus olfactory receptor consOR2 bound to S-carvone and in co... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-42791 | ||||||||||||
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Title | Consensus olfactory receptor consOR2 bound to S-carvone and in complex with mini-Gs trimeric protein | ||||||||||||
Map data | |||||||||||||
Sample |
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Keywords | Odorant / Olfaction / GPCR / Receptor / SIGNALING PROTEIN | ||||||||||||
Function / homology | Function and homology information G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / 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 / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits ...G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / 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 / 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 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / 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 / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / 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 / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||||||||
Biological species | synthetic construct (others) / Lama glama (llama) / Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||||||||
Authors | Billesboelle CB / Del Torrent CL / Manglik A | ||||||||||||
Funding support | United States, 3 items
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Citation | Journal: Nature / Year: 2024 Title: Engineered odorant receptors illuminate the basis of odour discrimination. Authors: Claire A de March / Ning Ma / Christian B Billesbølle / Jeevan Tewari / Claudia Llinas Del Torrent / Wijnand J C van der Velden / Ichie Ojiro / Ikumi Takayama / Bryan Faust / Linus Li / ...Authors: Claire A de March / Ning Ma / Christian B Billesbølle / Jeevan Tewari / Claudia Llinas Del Torrent / Wijnand J C van der Velden / Ichie Ojiro / Ikumi Takayama / Bryan Faust / Linus Li / Nagarajan Vaidehi / Aashish Manglik / Hiroaki Matsunami / Abstract: How the olfactory system detects and distinguishes odorants with diverse physicochemical properties and molecular configurations remains poorly understood. Vertebrate animals perceive odours through ...How the olfactory system detects and distinguishes odorants with diverse physicochemical properties and molecular configurations remains poorly understood. Vertebrate animals perceive odours through G protein-coupled odorant receptors (ORs). In humans, around 400 ORs enable the sense of smell. The OR family comprises two main classes: class I ORs are tuned to carboxylic acids whereas class II ORs, which represent most of the human repertoire, respond to a wide variety of odorants. A fundamental challenge in understanding olfaction is the inability to visualize odorant binding to ORs. Here we uncover molecular properties of odorant-OR interactions by using engineered ORs crafted using a consensus protein design strategy. Because such consensus ORs (consORs) are derived from the 17 major subfamilies of human ORs, they provide a template for modelling individual native ORs with high sequence and structural homology. The biochemical tractability of consORs enabled the determination of four cryogenic electron microscopy structures of distinct consORs with specific ligand recognition properties. The structure of a class I consOR, consOR51, showed high structural similarity to the native human receptor OR51E2 and generated a homology model of a related member of the human OR51 family with high predictive power. Structures of three class II consORs revealed distinct modes of odorant-binding and activation mechanisms between class I and class II ORs. Thus, the structures of consORs lay the groundwork for understanding molecular recognition of odorants by the OR superfamily. | ||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_42791.map.gz | 85.9 MB | EMDB map data format | |
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Header (meta data) | emd-42791-v30.xml emd-42791.xml | 19.3 KB 19.3 KB | Display Display | EMDB header |
Images | emd_42791.png | 72.1 KB | ||
Filedesc metadata | emd-42791.cif.gz | 6.5 KB | ||
Others | emd_42791_half_map_1.map.gz emd_42791_half_map_2.map.gz | 84.7 MB 84.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-42791 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-42791 | HTTPS FTP |
-Validation report
Summary document | emd_42791_validation.pdf.gz | 843.7 KB | Display | EMDB validaton report |
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Full document | emd_42791_full_validation.pdf.gz | 843.3 KB | Display | |
Data in XML | emd_42791_validation.xml.gz | 13.1 KB | Display | |
Data in CIF | emd_42791_validation.cif.gz | 15.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-42791 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-42791 | HTTPS FTP |
-Related structure data
Related structure data | 8uy0MC 8uxvC 8uxyC 8uyqC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_42791.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.86 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_42791_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_42791_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : consOR2-miniGs complex bound to Nb35
Entire | Name: consOR2-miniGs complex bound to Nb35 |
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Components |
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-Supramolecule #1: consOR2-miniGs complex bound to Nb35
Supramolecule | Name: consOR2-miniGs complex bound to Nb35 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 100 KDa |
-Macromolecule #1: consOR2
Macromolecule | Name: consOR2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 35.898629 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DYKDDDDASI DMEENQTSST DFILLGLFDH PRLELLLFVL ILLIYLLALL GNGLIILLIH LDSRLHTPMY FFLSQLSLMD LCYTSTTVP KMLVNLLSGD KTISFAGCGA QLFLYLTLGG TECLLLAVMA YDRYVAICHP LRYPVLMNPR VCLLLAAGSW L LGSLDSLI ...String: DYKDDDDASI DMEENQTSST DFILLGLFDH PRLELLLFVL ILLIYLLALL GNGLIILLIH LDSRLHTPMY FFLSQLSLMD LCYTSTTVP KMLVNLLSGD KTISFAGCGA QLFLYLTLGG TECLLLAVMA YDRYVAICHP LRYPVLMNPR VCLLLAAGSW L LGSLDSLI HTVLTLSLPF CGSREINHFF CEVPALLKLA CADTSLNETV MFVCCVLMLL IPLSLILVSY GRILLAVLRM QS AEGRRKA FSTCSSHLTV VGLFYGAAIY MYLQPKSYHS PEQDKVVSLF YTILTPMLNP LIYSLRNKEV KGALRRVLGK CRS L |
-Macromolecule #2: Nanobody 35
Macromolecule | Name: Nanobody 35 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Lama glama (llama) |
Molecular weight | Theoretical: 15.931698 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSSL EVLFQGPGHH HHHHHH |
-Macromolecule #3: miniGs399
Macromolecule | Name: miniGs399 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 30.137025 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: 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 |
-Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Macromolecule | Name: 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 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 40.786566 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: 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 |
-Macromolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Macromolecule | Name: 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 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Macromolecule #6: (5S)-2-methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-one
Macromolecule | Name: (5S)-2-methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-one / type: ligand / ID: 6 / Number of copies: 1 / Formula: 0WU |
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Molecular weight | Theoretical: 150.218 Da |
Chemical component information | ChemComp-0WU: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 105000 |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 131718 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |