[English] 日本語
Yorodumi- EMDB-27895: Mouse TRPM8 structure determined in the ligand- and PI(4,5)P2-fre... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-27895 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Mouse TRPM8 structure determined in the ligand- and PI(4,5)P2-free condition, Class I , C0 state | |||||||||
Map data | Full map, sharpened with B-factor -50 | |||||||||
Sample |
| |||||||||
Keywords | 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 | Function and homology information ligand-gated calcium channel activity / TRP channels / thermoception / response to temperature stimulus / response to cold / calcium ion transmembrane transport / calcium channel activity / intracellular calcium ion homeostasis / calcium ion transport / monoatomic ion channel activity ...ligand-gated calcium channel activity / TRP channels / thermoception / response to temperature stimulus / response to cold / calcium ion transmembrane transport / calcium channel activity / intracellular calcium ion homeostasis / calcium ion transport / monoatomic ion channel activity / positive regulation of cold-induced thermogenesis / membrane raft / external side of plasma membrane / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.59 Å | |||||||||
Authors | Yin Y / Zhang F / Feng S / Butay KJ / Borgnia MJ / Im W / Lee S-Y | |||||||||
Funding support | United States, 2 items
| |||||||||
Citation | Journal: Science / Year: 2022 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 |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_27895.map.gz | 64 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-27895-v30.xml emd-27895.xml | 19.1 KB 19.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_27895_fsc.xml | 11.9 KB | Display | FSC data file |
Images | emd_27895.png | 81 KB | ||
Masks | emd_27895_msk_1.map | 125 MB | Mask map | |
Filedesc metadata | emd-27895.cif.gz | 6.8 KB | ||
Others | emd_27895_half_map_1.map.gz emd_27895_half_map_2.map.gz | 115.6 MB 115.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-27895 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27895 | HTTPS FTP |
-Validation report
Summary document | emd_27895_validation.pdf.gz | 1 MB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_27895_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | emd_27895_validation.xml.gz | 19.4 KB | Display | |
Data in CIF | emd_27895_validation.cif.gz | 24.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27895 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27895 | HTTPS FTP |
-Related structure data
Related structure data | 8e4pMC 8e4lC 8e4mC 8e4nC 8e4oC 8e4qC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|
-Map
File | Download / File: emd_27895.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Full map, sharpened with B-factor -50 | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Mask #1
File | emd_27895_msk_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Half map A
File | emd_27895_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half map A | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Half map B
File | emd_27895_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half map B | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : Transient receptor potential cation channel subfamily M member 8
Entire | Name: Transient receptor potential cation channel subfamily M member 8 |
---|---|
Components |
|
-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 |
---|---|
Source (natural) | Organism: Mus musculus (house mouse) |
-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 |
---|---|
Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 131.548312 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MASFEGARLS MRSRRNGTMG STRTLYSSVS RSTDVSYSDS DLVNFIQANF KKRECVFFTR DSKAMENICK CGYAQSQHIE GTQINQNEK WNYKKHTKEF PTDAFGDIQF ETLGKKGKYL RLSCDTDSET LYELLTQHWH LKTPNLVISV TGGAKNFALK P RMRKIFSR ...String: MASFEGARLS MRSRRNGTMG STRTLYSSVS RSTDVSYSDS DLVNFIQANF KKRECVFFTR DSKAMENICK CGYAQSQHIE GTQINQNEK WNYKKHTKEF PTDAFGDIQF ETLGKKGKYL RLSCDTDSET LYELLTQHWH LKTPNLVISV TGGAKNFALK P RMRKIFSR LIYIAQSKGA WILTGGTHYG LMKYIGEVVR DNTISRNSEE NIVAIGIAAW GMVSNRDTLI RSCDDEGHFS AQ YIMDDFT RDPLYILDNN HTHLLLVDNG CHGHPTVEAK LRNQLEKYIS ERTSQDSNYG GKIPIVCFAQ GGGRETLKAI NTS VKSKIP CVVVEGSGQI ADVIASLVEV EDVLTSSMVK EKLVRFLPRT VSRLPEEEIE SWIKWLKEIL ESSHLLTVIK MEEA GDEIV SNAISYALYK AFSTNEQDKD NWNGQLKLLL EWNQLDLASD EIFTNDRRWE SADLQEVMFT ALIKDRPKFV RLFLE NGLN LQKFLTNEVL TELFSTHFST LVYRNLQIAK NSYNDALLTF VWKLVANFRR SFWKEDRSSR EDLDVELHDA SLTTRH PLQ ALFIWAILQN KKELSKVIWE QTKGCTLAAL GASKLLKTLA KVKNDINAAG ESEELANEYE TRAVELFTEC YSNDEDL AE QLLVYSCEAW GGSNCLELAV EATDQHFIAQ PGVQNFLSKQ WYGEISRDTK NWKIILCLFI IPLVGCGLVS FRKKPIDK H KKLLWYYVAF FTSPFVVFSW NVVFYIAFLL LFAYVLLMDF HSVPHTPELI LYALVFVLFC DEVRQWYMNG VNYFTDLWN VMDTLGLFYF IAGIVFRLHS SNKSSLYSGR VIFCLDYIIF TLRLIHIFTV SRNLGPKIIM LQRMLIDVFF FLFLFAVWMV AFGVARQGI LRQNEQRWRW IFRSVIYEPY LAMFGQVPSD VDSTTYDFSH CTFSGNESKP LCVELDEHNL PRFPEWITIP L VCIYMLST NILLVNLLVA MFGYTVGIVQ ENNDQVWKFQ RYFLVQEYCN RLNIPFPFVV FAYFYMVVKK CFKCCCKEKN ME SNACCFR NEDNETLAWE GVMKENYLVK INTKANDNSE EMRHRFRQLD SKLNDLKSLL KEIANNIKSN SLEVLFQGPD YKD DDDKAH HHHHHHHHH UniProtKB: Transient receptor potential cation channel subfamily M member 8 |
-Macromolecule #2: CHOLESTEROL HEMISUCCINATE
Macromolecule | Name: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 2 / Number of copies: 12 / Formula: Y01 |
---|---|
Molecular weight | Theoretical: 486.726 Da |
Chemical component information | ChemComp-Y01: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
---|---|
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: 293.15 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 1 / Number real images: 10147 / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.7000000000000001 µm / Nominal magnification: 81000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |