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Open data
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Basic information
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Title | Cryo-EM structure of a class T GPCR in active state | |||||||||||||||
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Function / homology | ![]() bitter taste receptor activity / detection of chemical stimulus involved in sensory perception of bitter taste / Class C/3 (Metabotropic glutamate/pheromone receptors) / ciliary membrane / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() | |||||||||||||||
Method | ![]() ![]() | |||||||||||||||
![]() | Liu ZJ / Hua T / Xu WX / Wu LJ | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for strychnine activation of human bitter taste receptor TAS2R46. Authors: Weixiu Xu / Lijie Wu / Shenhui Liu / Xiao Liu / Xiaoling Cao / Cui Zhou / Jinyi Zhang / You Fu / Yu Guo / Yiran Wu / Qiwen Tan / Ling Wang / Junlin Liu / Longquan Jiang / Zhongbo Fan / Yuan ...Authors: Weixiu Xu / Lijie Wu / Shenhui Liu / Xiao Liu / Xiaoling Cao / Cui Zhou / Jinyi Zhang / You Fu / Yu Guo / Yiran Wu / Qiwen Tan / Ling Wang / Junlin Liu / Longquan Jiang / Zhongbo Fan / Yuan Pei / Jingyi Yu / Jianjun Cheng / Suwen Zhao / Xiaojiang Hao / Zhi-Jie Liu / Tian Hua / ![]() Abstract: Taste sensing is a sophisticated chemosensory process, and bitter taste perception is mediated by type 2 taste receptors (TAS2Rs), or class T G protein-coupled receptors. Understanding the detailed ...Taste sensing is a sophisticated chemosensory process, and bitter taste perception is mediated by type 2 taste receptors (TAS2Rs), or class T G protein-coupled receptors. Understanding the detailed molecular mechanisms behind taste sensation is hindered by a lack of experimental receptor structures. Here, we report the cryo-electron microscopy structures of human TAS2R46 complexed with chimeric mini-G protein gustducin, in both strychnine-bound and apo forms. Several features of TAS2R46 are disclosed, including distinct receptor structures that compare with known GPCRs, a new "toggle switch," activation-related motifs, and precoupling with mini-G protein gustducin. Furthermore, the dynamic extracellular and more-static intracellular parts of TAS2R46 suggest possible diverse ligand-recognition and activation processes. This study provides a basis for further exploration of other bitter taste receptors and their therapeutic applications. | |||||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 57 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 22.6 KB 22.6 KB | Display Display | ![]() |
Images | ![]() | 47 KB | ||
Others | ![]() ![]() | 59.3 MB 59.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7xp6MC ![]() 7xp4C ![]() 7xp5C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.04 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_33366_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_33366_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Complex of GPCR and G protein
Entire | Name: Complex of GPCR and G protein |
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Components |
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-Supramolecule #1: Complex of GPCR and G protein
Supramolecule | Name: Complex of GPCR and G protein / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() ![]() |
-Macromolecule #1: Guanine nucleotide-binding protein G(t) subunit alpha-3
Macromolecule | Name: Guanine nucleotide-binding protein G(t) subunit alpha-3 type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 30.583334 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MDYKDDDDKE NLYFQSNSKT EDQRNEEKAQ REANKKIEKQ LQKDKQVYRA THRLLLLGAD NSGKSTIVKQ MRILHGGSGG SGGTSGIFE TKFQVDKVNF HMFDVGGQRD ERRKWIQCFN DVTAIIFVVD SSDYNRLQEA LNDFKSIWNN RWLRTISVIL F LNKQDLLA ...String: MDYKDDDDKE NLYFQSNSKT EDQRNEEKAQ REANKKIEKQ LQKDKQVYRA THRLLLLGAD NSGKSTIVKQ MRILHGGSGG SGGTSGIFE TKFQVDKVNF HMFDVGGQRD ERRKWIQCFN DVTAIIFVVD SSDYNRLQEA LNDFKSIWNN RWLRTISVIL F LNKQDLLA EKVLAGKSKI EDYFPEFARY TTPEDATPEP GEDPRVTRAK YFIRDEFLRI STASGDGRHY CYPHFTCAVD TQ NVKFVFD AVTDIIIKEN LKDCGLF |
-Macromolecule #2: 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: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 39.728426 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...String: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWNGSSGGG GSGGGGSSGV SGWRLFKKIS |
-Macromolecule #3: 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: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-Macromolecule #4: Nanobody 35
Macromolecule | Name: Nanobody 35 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 15.271938 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MQVQLQESGG GLVQPGGSLR LSCAASGFTF SNYKMNWVRQ APGKGLEWVS DISQSGASIS YTGSVKGRFT ISRDNAKNTL YLQMNSLKP EDTAVYYCAR CPAPFTRDCF DVTSTTYAYR GQGTQVTVSS HHHHHHEPEA |
-Macromolecule #5: Endoglucanase H,Taste receptor type 2 member 46,Endoglucanase H,T...
Macromolecule | Name: Endoglucanase H,Taste receptor type 2 member 46,Endoglucanase H,Taste receptor type 2 member 46,Bitter taste receptor T2R46 type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 91.116266 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MKTIIALSYI FCLVFADYKD DDDAHHHHHH HHHHENLYFQ SGRAMASNYN SGLKIGAWVG TQPSESAIKS FQELQGRKLD IVHQFINWS TDFSWVRPYA DAVYNNGSIL MITWEPWEYN TVDIKNGKAD AYITRMAQDM KAYGKEIWLR PLHAANGDWY P WAIGYSSR ...String: MKTIIALSYI FCLVFADYKD DDDAHHHHHH HHHHENLYFQ SGRAMASNYN SGLKIGAWVG TQPSESAIKS FQELQGRKLD IVHQFINWS TDFSWVRPYA DAVYNNGSIL MITWEPWEYN TVDIKNGKAD AYITRMAQDM KAYGKEIWLR PLHAANGDWY P WAIGYSSR VNTNETYIAA FRHIVDIFRA NGATNVKWVF NVNCDNVGNG TSYLGHYPGD NYVDYTSIDG YNWGTTQSWG SQ WQSFDQV FSRAYQALAS INKPIIIAEF ASAEIGGNKA RWITEAYNSI RTSYNKVIAA VWFHENKETD WRINSSPEAL AAY REAIGA ITFLPIIFSI LIVVTFVIGN FANGFIALVN SIEWFKRQKI SFADQILTAL AVSRVGLLWV LVLNWYATEL NPAF NSIEV RITAYNVWAV INHFSNWLAT SLSIFYLLKI ANFSNLIFLH LKRRVKSVVL VILLGPLLFL VCHLFVINMN QIIWT KEYE GNMTWKIKLR SAMYLSNTTV TILANLVPFT LTLISFLLLI CSLCKHLKKM QLHGKGSQDP SMKVHIKALQ TVTSFL LLC AIYFLSIIMS VWSFESLENK PVFMFCEAIA FSYPSTHPFI LIWGNKKLKQ TFLSVLWHVR YWVKGEKPSS SGSGSSG SG SSVFTLEDFV GDWEQTAAYN LDQVLEQGGV SSLLQNLAVS VTPIQRIVRS GENALKIDIH VIIPYEGLSA DQMAQIEE V FKVVYPVDDH HFKVILPYGT LVIDGVTPNM LNYFGRPYEG IAVFDGKKIT VTGTLWNGNK IIDERLITPD GSMLFRVTI NS |
-Macromolecule #6: STRYCHNINE
Macromolecule | Name: STRYCHNINE / type: ligand / ID: 6 / Number of copies: 1 / Formula: SY9 |
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Molecular weight | Theoretical: 334.412 Da |
Chemical component information | ![]() ChemComp-SY9: |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 400 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK II |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
CTF correction | Software - Name: cryoSPARC (ver. 3.3.1) |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final 3D classification | Number classes: 2 / Software - Name: cryoSPARC (ver. 3.3.1) |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.3.1) |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.01 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 161474 |
-Atomic model buiding 1
Refinement | Protocol: RIGID BODY FIT |
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Output model | ![]() PDB-7xp6: |