[English] 日本語
Yorodumi
- EMDB-73531: Cryo-EM structure of the L900V;R993P;S1060R mutant mouse TRPM4 ch... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-73531
TitleCryo-EM structure of the L900V;R993P;S1060R mutant mouse TRPM4 channel in an open state bound to NC1 and PI(4,5)P2.
Map data
Sample
  • Complex: mouse TRPM4
    • Protein or peptide: Transient receptor potential cation channel subfamily M member 4
  • Ligand: CALCIUM ION
  • 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: Necrocide 1
KeywordsTRPM4 / Ion channel / TRANSPORT PROTEIN
Biological speciesMus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.81 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
Citation
Journal: bioRxiv / Year: 2026
Title: Structural mechanism of Necrocide 1 activation of human TRPM4 that triggers necrosis by sodium overload.
Authors: Celso M Teixeira-Duarte / Wan Fu / Weizhong Zeng / Jianghuang Wang / Xinzhe Jiang / Ziye Zhao / Qing Zhong / Youxing Jiang /
Abstract: The small molecule Necrocide 1 (NC1) constitutively activates human TRPM4, triggering Na influx and leading to necrotic cell death, a process termed Necrosis by Sodium Overload (NECSO). NC1 ...The small molecule Necrocide 1 (NC1) constitutively activates human TRPM4, triggering Na influx and leading to necrotic cell death, a process termed Necrosis by Sodium Overload (NECSO). NC1 activation is specific to human TRPM4 and does not affect most of the other mammalian TRPM4 orthologs. Here, we elucidate the molecular mechanism underlying NC1 activation and its species-specific selectivity for human TRPM4 using a combination of single-particle cryo-EM, electrophysiology, and cell death assays. We identify the NC1-binding site and the key molecular determinants responsible for channel activation. In addition, we explain the insensitivity of mouse TRPM4 to NC1 and pinpoint specific residues that define NC1 specificity for human TRPM4. Given the upregulation of TRPM4 in various human cancers, our mechanistic insights into NC1 activation and specificity provide a framework for the potential development of cancer therapeutics targeting TRPM4-mediated necrosis.
#1: Journal: 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

-
Structure visualization

Supplemental images

emd_73531.png

Downloads & links

-
Map

FileDownload / File: emd_73531.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.74 Å/pix.
x 384 pix.
= 282.24 Å		0.74 Å/pix.
x 384 pix.
= 282.24 Å		0.74 Å/pix.
x 384 pix.
= 282.24 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.735 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy EMDB: 0.115
Minimum - Maximum-0.46923935 - 0.7926048
Average (Standard dev.)0.008229607 (±0.032283377)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 282.24 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_73531_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_73531_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : mouse TRPM4

EntireName: mouse TRPM4
Components
  • Complex: mouse TRPM4
    • Protein or peptide: Transient receptor potential cation channel subfamily M member 4
  • Ligand: CALCIUM ION
  • 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: Necrocide 1

-
Supramolecule #1: mouse TRPM4

SupramoleculeName: mouse TRPM4 / 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 4

MacromoleculeName: Transient receptor potential cation channel subfamily M member 4
type: protein_or_peptide / ID: 1 / Details: C terminal thrombin cleavage site and FLAG tag / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 137.654406 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MVGPEKEQSW IPKIFRKKVC TTFIVDLSDD AGGTLCQCGQ PRDAHPSVAV EDAFGAAVVT EWNSDEHTTE KPTDAYGDLD FTYSGRKHS NFLRLSDRTD PATVYSLVTR SWGFRAPNLV VSVLGGSGGP VLQTWLQDLL RRGLVRAAQS TGAWIVTGGL H TGIGRHVG ...String:
MVGPEKEQSW IPKIFRKKVC TTFIVDLSDD AGGTLCQCGQ PRDAHPSVAV EDAFGAAVVT EWNSDEHTTE KPTDAYGDLD FTYSGRKHS NFLRLSDRTD PATVYSLVTR SWGFRAPNLV VSVLGGSGGP VLQTWLQDLL RRGLVRAAQS TGAWIVTGGL H TGIGRHVG VAVRDHQTAS TGSSKVVAMG VAPWGVVRNR DMLINPKGSF PARYRWRGDP EDGVEFPLDY NYSAFFLVDD GT YGRLGGE NRFRLRFESY VAQQKTGVGG TGIDIPVLLL LIDGDEKMLK RIEDATQAQL PCLLVAGSGG AADCLVETLE DTL APGSGG LRRGEARDRI RRYFPKGDPE VLQAQVERIM TRKELLTVYS SEDGSEEFET IVLRALVKAC GSSEASAYLD ELRL AVAWN RVDIAQSELF RGDIQWRSFH LEASLMDALL NDRPEFVRLL ISHGLSLGHF LTPVRLAQLY SAVSPNSLIR NLLDQ ASHA SSSKSPPVNG TVELRPPNVG QVLRTLLGET CAPRYPARNT RDSYLGQDHR ENDSLLMDWA NKQPSTDASF EQAPWS DLL IWALLLNRAQ MAIYFWEKGS NSVASALGAC LLLRVMARLE SEAEEAARRK DLAATFESMS VDLFGECYHN SEERAAR LL LRRCPLWGEA TCLQLAMQAD ARAFFAQDGV QSLLTQKWWG EMDSTTPIWA LLLAFFCPPL IYTNLIVFRK SEEEPTQK D LDFDMDSSIN GAGPPGTVEP SAKVALERRQ RRRPGRALCC GKFSKRWSDF WGAPVTAFLG NVVSYLLFLL LFAHVLLVD FQPTKPSVSE LLLYFWAFTL LCEELRQGLG GGWGSLASGG RGPDRAPLRH RLHLYLSDTW NQCDLLALTC FLLGVGCRLT PGLFDLGRT VLCLDFMIFT VRLLHIFTVN KQLGPKIVIV SKMMKDVFFF LFFLCVWLVA YGVATEGILR PQDRSLPSIL R RVFYRPYL QIFGQIPQEE MDVALMIPGN CSMEPGSWAH PEGPVAGSCV SQYANWLVVL LLIVFLLVAN ILLLNLLIAM FS YTFSKVH GNSDLYWKAQ RYRLIREFHS RPALAPPLII ISHVRLLIKW LRRCRRCRRA NLPASPVFEH FRVCLSKEAE RKL LTWESV HKENFLLAQA RDKRDSDSER LKRTSQKVDT ALKQLGQIRE YDRRLRGLER EVQHCSRVLT WMAEALSHSA LLPP GAPPP PSPTGSKDLV PRGSGADYKD DDDK

UniProtKB: Transient receptor potential cation channel subfamily M member 4

-
Macromolecule #2: CALCIUM ION

MacromoleculeName: CALCIUM ION / type: ligand / ID: 2 / Number of copies: 4 / Formula: CA
Molecular weightTheoretical: 40.078 Da

-
Macromolecule #3: [(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: 3 / Number of copies: 4 / Formula: PT5
Molecular weightTheoretical: 1.047088 KDa

-
Macromolecule #4: Necrocide 1

MacromoleculeName: Necrocide 1 / type: ligand / ID: 4 / Number of copies: 4 / Formula: A1CY8
Molecular weightTheoretical: 365.465 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k 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

+
Image processing

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

6bcj

Final reconstructionApplied symmetry - Point group: C4 (4 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 2.81 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 19675
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

-
Atomic model buiding 1

SoftwareName: Coot (ver. 1.1.18)
Output model

PDB-9yvp:
Cryo-EM structure of the L900V;R993P;S1060R mutant mouse TRPM4 channel in an open state bound to NC1 and PI(4,5)P2.

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more