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- EMDB-27896: The closed C0-state flycatcher TRPM8 structure in complex with PI... -
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Open data
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Basic information
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Title | The closed C0-state flycatcher TRPM8 structure in complex with PI(4,5)P2 | |||||||||
![]() | Full map, sharpened with B-factor -50 | |||||||||
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![]() | TRPM8 / menthol receptor / cold receptor / cold sensor / PI(4 / 5)P2 / cooling agonists / temperature sensing / ion channel / sensory transduction / transient receptor potential ion channel / MEMBRANE PROTEIN | |||||||||
Function / homology | ligand-gated calcium channel activity / TRPM, SLOG domain / SLOG in TRPM / Ion transport domain / Ion transport protein / identical protein binding / membrane / Transient receptor potential cation channel subfamily M member 8![]() | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.51 Å | |||||||||
![]() | Yin Y / Zhang F / Feng S / Butay KJ / Borgnia MJ / Im W / Lee S-Y | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Activation mechanism of the mouse cold-sensing TRPM8 channel by cooling agonist and PIP. Authors: Ying Yin / Feng Zhang / Shasha Feng / Kevin John Butay / Mario J Borgnia / Wonpil Im / Seok-Yong Lee / ![]() Abstract: The transient receptor potential melastatin 8 (TRPM8) channel is the primary molecular transducer responsible for the cool sensation elicited by menthol and cold in mammals. TRPM8 activation is ...The transient receptor potential melastatin 8 (TRPM8) channel is the primary molecular transducer responsible for the cool sensation elicited by menthol and cold in mammals. TRPM8 activation is controlled by cooling compounds together with the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP). Our knowledge of cold sensation and the therapeutic potential of TRPM8 for neuroinflammatory diseases and pain will be enhanced by understanding the structural basis of cooling agonist- and PIP-dependent TRPM8 activation. We present cryo-electron microscopy structures of mouse TRPM8 in closed, intermediate, and open states along the ligand- and PIP-dependent gating pathway. Our results uncover two discrete agonist sites, state-dependent rearrangements in the gate positions, and a disordered-to-ordered transition of the gate-forming S6-elucidating the molecular basis of chemically induced cool sensation in mammals. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 32.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19 KB 19 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.6 KB | Display | ![]() |
Images | ![]() | 27.3 KB | ||
Masks | ![]() | 64 MB | ![]() | |
Filedesc metadata | ![]() | 6.8 KB | ||
Others | ![]() ![]() | 59 MB 59 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 976.8 KB | Display | ![]() |
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Full document | ![]() | 976.3 KB | Display | |
Data in XML | ![]() | 16.3 KB | Display | |
Data in CIF | ![]() | 21.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8e4qMC ![]() 8e4lC ![]() 8e4mC ![]() 8e4nC ![]() 8e4oC ![]() 8e4pC 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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Map
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Annotation | Full map, sharpened with B-factor -50 | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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Density Histograms |
-Half map: Half map A
File | emd_27896_half_map_1.map | ||||||||||||
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Annotation | Half map A | ||||||||||||
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Density Histograms |
-Half map: Half map B
File | emd_27896_half_map_2.map | ||||||||||||
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Annotation | Half map B | ||||||||||||
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Sample components
-Entire : Transient receptor potential cation channel subfamily M member 8
Entire | Name: Transient receptor potential cation channel subfamily M member 8 |
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Components |
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-Supramolecule #1: Transient receptor potential cation channel subfamily M member 8
Supramolecule | Name: Transient receptor potential cation channel subfamily M member 8 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Transient receptor potential cation channel subfamily M member 8
Macromolecule | Name: Transient receptor potential cation channel subfamily M member 8 type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 131.343406 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MATLFQVSMG SMRHRRNGNF ESSRLLYSSM SRSIDVACSD ADLANFIQEN FKKRECVFFT KDTKSMGNLC KCGYPENQHI EGTQVNTTE KWNYKKHTKE LPTDAFGDIQ FENLGKRGKY IRLSCDTDSE TLYDLMTQHW HLKTPNLVIS VTGGAKNFAL K PRMRKIFS ...String: MATLFQVSMG SMRHRRNGNF ESSRLLYSSM SRSIDVACSD ADLANFIQEN FKKRECVFFT KDTKSMGNLC KCGYPENQHI EGTQVNTTE KWNYKKHTKE LPTDAFGDIQ FENLGKRGKY IRLSCDTDSE TLYDLMTQHW HLKTPNLVIS VTGGAKNFAL K PRMRKIFS RLIYIAQSKG AWIFTGGTHY GLMKYIGEVV RDNTISRSSE ENVVAIGIAA WGMISNRETL IRTADSDGSY LA HYIMDDL KRDPLYCLDN NHTHLLLVDN GTHGHPTIEA KVRTQLEKYI SERVIPESNY GGKIPIVCFA QGGGKETLKS INV AIKSKI PCVVVEGSGR IADVIASLVE AEGTLASSCV KESLLRFLPR TISRLSEEET ESWIKWIKEV LESPHLLTVI KIEE AGDEI VSNAISFALY KAFSTNEHDR DNWNGQLKLL LEWNQLDLAS DEIFTNDRNW ESADLQDVMF TALVKDRPKF VRLFL ENGL NLRKFLTTEV LRELYTNNFS SLVFKNLQIA KNSYNDALLT FVWKMVEDFR RGAKRDDKNS KDEMEIELSE ECPITR HPL QALFIWSVLQ NKKELSKVIW EQTRGCTLAA LGASKLLKSM AKVKNDINAA GESEELANEY ETRAVELFTE CYSNDED LA EQLLTYSCEA WGGSNCLELA VEARDQQFIA QPGVQNFLSK QWYGEISRDT KNWKIILCLF FFPLIGCGFI SFRKKPVE K TKKLFLYYVS FFTSPFVVFS WNVIFYIAFL LLFAYVLLMD FQKEPTALEI ILYVLVFILL CDEVRQWYMN GSKYFSDLW NVMDTLAIFY FIAGIVFRLH SDESSWYSGR VIFCLDYIVF TLRLIHIFTV SRNLGPKIIM LQRMMIDVFF FLFLFAVWMV AFGVARQGI LRKNEHRWEW IFRSVIYEPY LAMFGQYPDD IDGTTYNFDH CTFSGNESKP LCVELDANNQ PRFPEWITIP L VCIYMLST NILLVNLLVA MFGYTVGSVQ ENNDQVWKFQ RFFLVQEYCS RLTIPFPFVI FAYIFMVMRK CFKCCCKKES KE PSVCCSR NEDNEILAWE AVMKENYLVK INTKASDSSE EMVHRFRQLD AKLSDLKGLL KEISSKIKSN SLEVLFQGPD YKD DDDKAH HHHHHHHHH UniProtKB: Transient receptor potential cation channel subfamily M member 8 |
-Macromolecule #2: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(o...
Macromolecule | Name: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate type: ligand / ID: 2 / Number of copies: 4 / Formula: PIO |
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Molecular weight | Theoretical: 746.566 Da |
Chemical component information | ![]() ChemComp-PIO: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 2 / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 4283 / Average electron dose: 42.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.25 µm / Nominal magnification: 75000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |