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- PDB-8e4q: The closed C0-state flycatcher TRPM8 structure in complex with PI... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8e4q | |||||||||
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Title | The closed C0-state flycatcher TRPM8 structure in complex with PI(4,5)P2 | |||||||||
![]() | Transient receptor potential cation channel subfamily M member 8 | |||||||||
![]() | MEMBRANE PROTEIN / TRPM8 / menthol receptor / cold receptor / cold sensor / PI(4 / 5)P2 / cooling agonists / temperature sensing / ion channel / sensory transduction / transient receptor potential ion channel | |||||||||
Function / homology | ![]() ligand-gated calcium channel activity / identical protein binding / membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.51 Å | |||||||||
![]() | Yin, Y. / Zhang, F. / Feng, S. / Butay, K.J. / Borgnia, M.J. / 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
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 1.1 MB | Display | ![]() |
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PDB format | ![]() | 923.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 27896MC ![]() 8e4lC ![]() 8e4mC ![]() 8e4nC ![]() 8e4oC ![]() 8e4pC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 131343.406 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Production host: ![]() #2: Chemical | ChemComp-PIO / [( Has ligand of interest | Y | Sequence details | As per the authors, the old version of Uniprot U3JD03 was used for gene synthesis of the sample sequence | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Transient receptor potential cation channel subfamily M member 8 Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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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: 277.15 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 75000 X / Nominal defocus max: 3000 nm / Nominal defocus min: 1250 nm / Cs: 2.7 mm / C2 aperture diameter: 70 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 42 e/Å2 / Detector mode: COUNTING / Film or detector model: FEI FALCON III (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 4283 |
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Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | |||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1308147 | |||||||||||||||||||||||||||
Symmetry | Point symmetry: C4 (4 fold cyclic) | |||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.51 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 51879 / Symmetry type: POINT | |||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | |||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6NR2 Accession code: 6NR2 / Source name: PDB / Type: experimental model | |||||||||||||||||||||||||||
Refine LS restraints |
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