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- EMDB-73527: Cryo-EM structure of the human TRPM4 channel in an open state bou... -

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Basic information

Entry
Database: EMDB / ID: EMD-73527
TitleCryo-EM structure of the human TRPM4 channel in an open state bound to NC1 and PI(4,5)P2.
Map data
Sample
  • Complex: human TRPM4
    • Protein or peptide: Transient receptor potential cation channel subfamily M member 4
  • Ligand: [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phospho ryl]oxy-propan-2-yl] (8Z)-icosa-5,8,11,14-tetraenoate
  • Ligand: CALCIUM ION
  • Ligand: Necrocide 1
KeywordsTRPM4 / Ion channel / TRANSPORT PROTEIN
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.78 Å
AuthorsTeixeira-Duarte CM / Jiang Y
Funding support United States, 3 items
OrganizationGrant numberCountry
Howard Hughes Medical Institute (HHMI) United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35 GM140892 United States
Welch FoundationI-1578 United States
CitationJournal: Nat Commun / Year: 2026
Title: Structural mechanism of Necrocide 1 activation of human TRPM4 that triggers necrosis by sodium overload
Authors: Teixeira-Duarte CM / Fu W / Zeng W / Wang J / Jiang X / Zhao Z / Zhong Q / Jiang Y
History
DepositionOct 23, 2025-
Header (metadata) releaseJul 1, 2026-
Map releaseJul 1, 2026-
UpdateJul 1, 2026-
Current statusJul 1, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_73527.png

Downloads & links

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Map

FileDownload / File: emd_73527.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 300 pix.
= 250.32 Å		0.83 Å/pix.
x 300 pix.
= 250.32 Å		0.83 Å/pix.
x 300 pix.
= 250.32 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.8344 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.45
Minimum - Maximum-1.0478944 - 2.3738797
Average (Standard dev.)0.039926555 (±0.1009749)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 250.31999 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_73527_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_73527_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 : human TRPM4

EntireName: human TRPM4
Components
  • Complex: human TRPM4
    • Protein or peptide: Transient receptor potential cation channel subfamily M member 4
  • Ligand: [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phospho ryl]oxy-propan-2-yl] (8Z)-icosa-5,8,11,14-tetraenoate
  • Ligand: CALCIUM ION
  • Ligand: Necrocide 1

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Supramolecule #1: human TRPM4

SupramoleculeName: human TRPM4 / 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 4

MacromoleculeName: Transient receptor potential cation channel subfamily M member 4
type: protein_or_peptide / ID: 1 / Details: N terminal FLAG tag and thrombin cleavage site / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 136.265359 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MDYKDDDDKG SGLVPRGSVV PEKEQSWIPK IFKKKTCTTF IVDSTDPGGT LCQCGRPRTA HPAVAMEDAF GAAVVTVWDS DAHTTEKPT DAYGELDFTG AGRKHSNFLR LSDRTDPAAV YSLVTRTWGF RAPNLVVSVL GGSGGPVLQT WLQDLLRRGL V RAAQSTGA ...String:
MDYKDDDDKG SGLVPRGSVV PEKEQSWIPK IFKKKTCTTF IVDSTDPGGT LCQCGRPRTA HPAVAMEDAF GAAVVTVWDS DAHTTEKPT DAYGELDFTG AGRKHSNFLR LSDRTDPAAV YSLVTRTWGF RAPNLVVSVL GGSGGPVLQT WLQDLLRRGL V RAAQSTGA WIVTGGLHTG IGRHVGVAVR DHQMASTGGT KVVAMGVAPW GVVRNRDTLI NPKGSFPARY RWRGDPEDGV QF PLDYNYS AFFLVDDGTH GCLGGENRFR LRLESYISQQ KTGVGGTGID IPVLLLLIDG DEKMLTRIEN ATQAQLPCLL VAG SGGAAD CLAETLEDTL APGSGGARQG EARDRIRRFF PKGDLEVLQA QVERIMTRKE LLTVYSSEDG SEEFETIVLK ALVK ACGSS EASAYLDELR LAVAWNRVDI AQSELFRGDI QWRSFHLEAS LMDALLNDRP EFVRLLISHG LSLGHFLTPM RLAQL YSAA PSNSLIRNLL DQASHSAGTK APALKGGAAE LRPPDVGHVL RMLLGKMCAP RYPSGGAWDP HPGQGFGESM YLLSDK ATS PLSLDAGLGQ APWSDLLLWA LLLNRAQMAM YFWEMGSNAV SSALGACLLL RVMARLEPDA EEAARRKDLA FKFEGMG VD LFGECYRSSE VRAARLLLRR CPLWGDATCL QLAMQADARA FFAQDGVQSL LTQKWWGDMA STTPIWALVL AFFCPPLI Y TRLITFRKSE EEPTREELEF DMDSVINGEG PVGTADPAEK TPLGVPRQSG RPGCCGGRCG GRRCLRRWFH FWGAPVTIF MGNVVSYLLF LLLFSRVLLV DFQPAPPGSL ELLLYFWAFT LLCEELRQGL SGGGGSLASG GPGPGHASLS QRLRLYLADS WNQCDLVAL TCFLLGVGCR LTPGLYHLGR TVLCIDFMVF TVRLLHIFTV NKQLGPKIVI VSKMMKDVFF FLFFLGVWLV A YGVATEGL LRPRDSDFPS ILRRVFYRPY LQIFGQIPQE DMDVALMEHS NCSSEPGFWA HPPGAQAGTC VSQYANWLVV LL LVIFLLV ANILLVNLLI AMFSYTFGKV QGNSDLYWKA QRYRLIREFH SRPALAPPFI VISHLRLLLR QLCRRPRSPQ PSS PALEHF RVYLSKEAER KLLTWESVHK ENFLLARARD KRESDSERLK RTSQKVDLAL KQLGHIREYE QRLKVLEREV QQCS RVLGW VAEALSRSAL LPPGGPPPPD LPGSKD

UniProtKB: Transient receptor potential cation channel subfamily M member 4

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Macromolecule #2: [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tr...

MacromoleculeName: [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phospho ryl]oxy-propan-2-yl] (8Z)-icosa-5,8,11,14-tetraenoate
type: ligand / ID: 2 / Number of copies: 4 / Formula: PT5
Molecular weightTheoretical: 1.047088 KDa

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Macromolecule #3: CALCIUM ION

MacromoleculeName: CALCIUM ION / type: ligand / ID: 3 / Number of copies: 4 / Formula: CA
Molecular weightTheoretical: 40.078 Da

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Macromolecule #4: Necrocide 1

MacromoleculeName: Necrocide 1 / type: ligand / ID: 4 / Number of copies: 4 / Formula: A1CY8
Molecular weightTheoretical: 365.465 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: 7.5
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.9 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

9mrt

Final reconstructionApplied symmetry - Point group: C4 (4 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 2.78 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 32516
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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Atomic model buiding 1

SoftwareName: Coot (ver. 1.1.18)
Output model

PDB-9yvl:
Cryo-EM structure of the human TRPM4 channel in an open state bound to NC1 and PI(4,5)P2.

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