[English] 日本語
![](img/lk-miru.gif)
- PDB-9b6f: Cryo-EM structure of the mouse TRPM8 channel in complex with the ... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 9b6f | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of the mouse TRPM8 channel in complex with the antagonist AMG2850 | |||||||||
![]() | Transient receptor potential cation channel subfamily M member 8 | |||||||||
![]() | MEMBRANE PROTEIN / TRPM8 / menthol receptor / cold receptor / PI(4 / 5)P2 / cooling agonists / temperature sensing / ion channel / sensory transduction / transient receptor potential ion channel / TRPM8 activation / TRPM8 inhibition / TRPM8 desensitization / TRPM8 antagonists | |||||||||
Function / homology | ![]() 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 | ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.42 Å | |||||||||
![]() | Yin, Y. / Park, C.-G. / Zhang, F. / Fedor, J. / Feng, S. / Suo, Y. / Im, W. / Lee, S.-Y. | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() Title: Mechanisms of sensory adaptation and inhibition of the cold and menthol receptor TRPM8. Authors: Ying Yin / Cheon-Gyu Park / Feng Zhang / Justin G Fedor / Shasha Feng / Yang Suo / Wonpil Im / Seok-Yong Lee / ![]() Abstract: Our sensory adaptation to cold and chemically induced coolness is mediated by the intrinsic property of TRPM8 channels to desensitize. TRPM8 is also implicated in cold-evoked pain disorders and ...Our sensory adaptation to cold and chemically induced coolness is mediated by the intrinsic property of TRPM8 channels to desensitize. TRPM8 is also implicated in cold-evoked pain disorders and migraine, highlighting its inhibitors as an avenue for pain relief. Despite the importance, the mechanisms of TRPM8 desensitization and inhibition remained unclear. We found, using cryo-electron microscopy, electrophysiology, and molecular dynamics simulations, that TRPM8 inhibitors bind selectively to the desensitized state of the channel. These inhibitors were used to reveal the overlapping mechanisms of desensitization and inhibition and that cold and cooling agonists share a common desensitization pathway. Furthermore, we identified the structural determinants crucial for the conformational change in TRPM8 desensitization. Our study illustrates how receptor-level conformational changes alter cold sensation, providing insights into therapeutic development. | |||||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 1.3 MB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 44257MC ![]() 9b6dC ![]() 9b6eC ![]() 9b6gC ![]() 9b6hC ![]() 9b6iC ![]() 9b6jC ![]() 9b6kC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | Mass: 131548.312 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Chemical | ChemComp-Y01 / #3: Chemical | ChemComp-A1AIY / ( Mass: 417.348 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C19H17F6N3O Has ligand of interest | Y | |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: Transient receptor potential cation channel subfamily M member 8 Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 293.15 K |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 81000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 700 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 53 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 9395 |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
-
Processing
EM software |
| |||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||
Particle selection | Num. of particles selected: 2608765 | |||||||||||||||||||||
Symmetry | Point symmetry: C4 (4 fold cyclic) | |||||||||||||||||||||
3D reconstruction | Resolution: 3.42 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 84589 / Symmetry type: POINT | |||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | |||||||||||||||||||||
Atomic model building | Details: Another structural model from this study was used as the initial model for model building. Source name: Other / Type: experimental model |