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- EMDB-71454: Human TRPM8 menthol bound structure at 4 degrees Celsius resolved... -

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ID or keywords:

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Basic information

Entry
Database: EMDB / ID: EMD-71454
TitleHuman TRPM8 menthol bound structure at 4 degrees Celsius resolved in cell vesicles using cryo-EM
Map data
Sample
  • Complex: Homotetrameric complex of human TRPM8 bound to menthol determined in cell-derived vesicles.
    • Protein or peptide: Transient receptor potential cation channel subfamily M member 8
  • Ligand: (1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexan-1-ol
KeywordsTRPM8 / transient receptor potential melastatin 8 / MEMBRANE PROTEIN / Human / menthol
Function / homology
Function and homology information


thermoception / ligand-gated calcium channel activity / TRP channels / plasma membrane raft / response to cold / calcium ion transmembrane transport / calcium channel activity / intracellular calcium ion homeostasis / positive regulation of cold-induced thermogenesis / external side of plasma membrane ...thermoception / ligand-gated calcium channel activity / TRP channels / plasma membrane raft / response to cold / calcium ion transmembrane transport / calcium channel activity / intracellular calcium ion homeostasis / positive regulation of cold-induced thermogenesis / external side of plasma membrane / endoplasmic reticulum membrane / metal ion binding / identical protein binding / plasma membrane
Similarity search - Function
: / TRPM, SLOG domain / : / SLOG in TRPM / TRPM2-like domain / Ion transport domain / Ion transport protein
Similarity search - Domain/homology
Transient receptor potential cation channel subfamily M member 8
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.5 Å
AuthorsChoi KY / Lin X / Cheng Y / Julius D
Funding support United States, 3 items
OrganizationGrant numberCountry
Howard Hughes Medical Institute (HHMI) United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)R35NS105038 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35GM140847 United States
CitationJournal: Nature / Year: 2026
Title: Structural energetics of cold sensitivity
Authors: Choi KY / Lin X / Cheng Y / Julius D
History
DepositionJun 26, 2025-
Header (metadata) releaseMar 25, 2026-
Map releaseMar 25, 2026-
UpdateMar 25, 2026-
Current statusMar 25, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_71454.png

Downloads & links

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Map

FileDownload / File: emd_71454.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.94 Å/pix.
x 288 pix.
= 270.72 Å		0.94 Å/pix.
x 288 pix.
= 270.72 Å		0.94 Å/pix.
x 288 pix.
= 270.72 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.94 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.08
Minimum - Maximum-0.83402157 - 1.2750583
Average (Standard dev.)0.0023245343 (±0.033909265)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions288288288
Spacing288288288
CellA=B=C: 270.72 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: #1

Fileemd_71454_additional_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_71454_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_71454_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Homotetrameric complex of human TRPM8 bound to menthol determined...

EntireName: Homotetrameric complex of human TRPM8 bound to menthol determined in cell-derived vesicles.
Components
  • Complex: Homotetrameric complex of human TRPM8 bound to menthol determined in cell-derived vesicles.
    • Protein or peptide: Transient receptor potential cation channel subfamily M member 8
  • Ligand: (1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexan-1-ol

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Supramolecule #1: Homotetrameric complex of human TRPM8 bound to menthol determined...

SupramoleculeName: Homotetrameric complex of human TRPM8 bound to menthol determined in cell-derived vesicles.
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Transient receptor potential cation channel subfamily M member 8

MacromoleculeName: Transient receptor potential cation channel subfamily M member 8
type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 128.334219 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: GPGSGSGMSF RAARLSMRNR RNDTLDSTRT LYSSASRSTD LSYSESDLVN FIQANFKKRE CVFFTKDSKA TENVCKCGYA QSQHMEGTQ INQSEKWNYK KHTKEFPTDA FGDIQFETLG KKGKYIRLSC DTDAEILYEL LTQHWHLKTP NLVISVTGGA K NFALKPRM ...String:
GPGSGSGMSF RAARLSMRNR RNDTLDSTRT LYSSASRSTD LSYSESDLVN FIQANFKKRE CVFFTKDSKA TENVCKCGYA QSQHMEGTQ INQSEKWNYK KHTKEFPTDA FGDIQFETLG KKGKYIRLSC DTDAEILYEL LTQHWHLKTP NLVISVTGGA K NFALKPRM RKIFSRLIYI AQSKGAWILT GGTHYGLMKY IGEVVRDNTI SRSSEENIVA IGIAAWGMVS NRDTLIRNCD AE GYFLAQY LMDDFTRDPL YILDNNHTHL LLVDNGCHGH PTVEAKLRNQ LEKYISERTI QDSNYGGKIP IVCFAQGGGK ETL KAINTS IKNKIPCVVV EGSGQIADVI ASLVEVEDAL TSSAVKEKLV RFLPRTVSRL PEEETESWIK WLKEILECSH LLTV IKMEE AGDEIVSNAI SYALYKAFST SEQDKDNWNG QLKLLLEWNQ LDLANDEIFT NDRRWESADL QEVMFTALIK DRPKF VRLF LENGLNLRKF LTHDVLTELF SNHFSTLVYR NLQIAKNSYN DALLTFVWKL VANFRRGFRK EDRNGRDEMD IELHDV SPI TRHPLQALFI WAILQNKKEL SKVIWEQTRG CTLAALGASK LLKTLAKVKN DINAAGESEE LANEYETRAV ELFTECY SS DEDLAEQLLV YSCEAWGGSN CLELAVEATD QHFIAQPGVQ NFLSKQWYGE ISRDTKNWKI ILCLFIIPLV GCGFVSFR K KPVDKHKKLL WYYVAFFTSP FVVFSWNVVF YIAFLLLFAY VLLMDFHSVP HPPELVLYSL VFVLFCDEVR QWYVNGVNY FTDLWNVMDT LGLFYFIAGI VFRLHSSNKS SLYSGRVIFC LDYIIFTLRL IHIFTVSRNL GPKIIMLQRM LIDVFFFLFL FAVWMVAFG VARQGILRQN EQRWRWIFRS VIYEPYLAMF GQVPSDVDGT TYDFAHCTFT GNESKPLCVE LDEHNLPRFP E WITIPLVC IYMLSTNILL VNLLVAMFGY TVGTVQENND QVWKFQRYFL VQEYCSRLNI PFPFIVFAYF YMVVKKCFKC CC KEKNMES SVCCFKNEDN ETLAWEGVMK ENYLVKINTK ANDTSEEMRH RFRQLDTKLN DLKGLLKEIA NKIK

UniProtKB: Transient receptor potential cation channel subfamily M member 8

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Macromolecule #2: (1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexan-1-ol

MacromoleculeName: (1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexan-1-ol / type: ligand / ID: 2 / Number of copies: 4 / Formula: XUQ
Molecular weightTheoretical: 156.265 Da

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
Component:
ConcentrationFormulaName
300.0 mMKClpotassium chloride
20.0 mMC8H18N2O4SHEPES
0.5 mMC13H17F13NO4PFos-Choline-8, Fluorinated
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Support film - Material: CARBON / Support film - topology: CONTINUOUS
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS KRIOS
Specialist opticsEnergy filter - Name: TFS Selectris X / Energy filter - Slit width: 6 eV
Image recordingFilm or detector model: TFS FALCON 4i (4k x 4k) / Number grids imaged: 1 / Number real images: 17737 / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 130000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 484131
CTF correctionSoftware - Name: cryoSPARC (ver. 4) / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER
Details: Model generated ab initio from screening dataset was used for subsequent refinement.
Final reconstructionApplied symmetry - Point group: C4 (4 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 101753
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4)

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