[English] 日本語
Yorodumi
- EMDB-73760: Cryo-EM structure of human TRPM4 channel in complex with EGTA and... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-73760
TitleCryo-EM structure of human TRPM4 channel in complex with EGTA and NC1 at 37 degrees Celsius (consensus)
Map data
Sample
  • Complex: human TRPM4 channel in complex with EGTA and NC1 at 37 degrees Celsius
    • Protein or peptide: Transient receptor potential cation channel subfamily M member 4
  • Ligand: Necrocide 1
Keywordsion channel / TRP channel / MEMBRANE PROTEIN
Function / homology
Function and homology information


positive regulation of atrial cardiac muscle cell action potential / positive regulation of regulation of vascular associated smooth muscle cell membrane depolarization / sodium channel complex / regulation of T cell cytokine production / negative regulation of bone mineralization / membrane depolarization during AV node cell action potential / membrane depolarization during bundle of His cell action potential / membrane depolarization during Purkinje myocyte cell action potential / metal ion transport / regulation of ventricular cardiac muscle cell action potential ...positive regulation of atrial cardiac muscle cell action potential / positive regulation of regulation of vascular associated smooth muscle cell membrane depolarization / sodium channel complex / regulation of T cell cytokine production / negative regulation of bone mineralization / membrane depolarization during AV node cell action potential / membrane depolarization during bundle of His cell action potential / membrane depolarization during Purkinje myocyte cell action potential / metal ion transport / regulation of ventricular cardiac muscle cell action potential / calcium-activated cation channel activity / sodium ion import across plasma membrane / dendritic cell chemotaxis / TRP channels / sodium channel activity / cellular response to ATP / regulation of heart rate by cardiac conduction / monoatomic cation transmembrane transport / positive regulation of fat cell differentiation / protein sumoylation / positive regulation of vasoconstriction / negative regulation of osteoblast differentiation / positive regulation of heart rate / positive regulation of adipose tissue development / positive regulation of insulin secretion involved in cellular response to glucose stimulus / calcium-mediated signaling / calcium ion transmembrane transport / calcium channel activity / transmembrane transport / positive regulation of canonical Wnt signaling pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / positive regulation of cytosolic calcium ion concentration / protein homotetramerization / adaptive immune response / calmodulin binding / neuronal cell body / positive regulation of cell population proliferation / calcium ion binding / Golgi apparatus / endoplasmic reticulum / ATP binding / membrane / 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 4
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.58 Å
AuthorsHu J / Lu W / Du J
Funding support United States, 9 items
OrganizationGrant numberCountry
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)R01HL153219 United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)R01NS129804 United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)R01NS111031 United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)R01NS112363 United States
Other privateMcKnight Scholar Award
Other privateKlingenstein-Simon Scholar Award
Other privateSloan Research Fellowship
Other privatePew Scholar in the Biomedical Sciences
American Heart Association24POST1196982 United States
CitationJournal: Nat Struct Mol Biol / Year: 2026
Title: Temperature and intrinsic Ca reshape TRPM4 pharmacology.
Authors: Jinhong Hu / Sofia Ievleva / Sung Jin Park / Junuk Lee / Jie Cheng / Garrett O'Dea / Jiangnan Sheng / Juan Du / Wei Lü /
Abstract: Proteins operate in dynamic environments where ions, lipids and temperature collectively define their properties, yet most studies rely on simplified conditions that overlook these intrinsic ...Proteins operate in dynamic environments where ions, lipids and temperature collectively define their properties, yet most studies rely on simplified conditions that overlook these intrinsic variables. Here we show two such factors-temperature and Ca-remodel the function and pharmacology of TRPM4, an ion channel implicated in cardiac conduction, immune regulation, cancer and intestinal-fluid homeostasis. At physiological temperature and Ca, TPPO-previously considered a selective TRPM5 inhibitor inactive toward TRPM4-potently activates TRPM4, revealing strong synergy among temperature, Ca and ligand binding. By contrast, Necrocide-1, a necroptotic activator targeting the same binding pocket, defies this logic: it opens TRPM4 without Ca but is antagonized by Ca. Meanwhile, the inhibitors NBA and CBA engage a nearby pocket, locking the channel in a non-conductive pre-open state. Our findings highlight that even rigid binding pockets can exhibit temperature-dependent ligand recognition, revealing hidden pharmacology and informing selective, environment-aware therapeutic strategies.
History
DepositionNov 4, 2025-
Header (metadata) releaseJun 10, 2026-
Map releaseJun 10, 2026-
UpdateJul 1, 2026-
Current statusJul 1, 2026Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_73760.png

Downloads & links

-
Map

FileDownload / File: emd_73760.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.)
0.87 Å/pix.
x 384 pix.
= 334.08 Å		0.87 Å/pix.
x 384 pix.
= 334.08 Å		0.87 Å/pix.
x 384 pix.
= 334.08 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.87 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.08
Minimum - Maximum-0.17064703 - 0.44461754
Average (Standard dev.)-0.000970075 (±0.016342573)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 334.08002 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Additional map: sharpened map

Fileemd_73760_additional_1.map
Annotationsharpened map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_73760_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_73760_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : human TRPM4 channel in complex with EGTA and NC1 at 37 degrees Celsius

EntireName: human TRPM4 channel in complex with EGTA and NC1 at 37 degrees Celsius
Components
  • Complex: human TRPM4 channel in complex with EGTA and NC1 at 37 degrees Celsius
    • Protein or peptide: Transient receptor potential cation channel subfamily M member 4
  • Ligand: Necrocide 1

-
Supramolecule #1: human TRPM4 channel in complex with EGTA and NC1 at 37 degrees Celsius

SupramoleculeName: human TRPM4 channel in complex with EGTA and NC1 at 37 degrees Celsius
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

-
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 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 134.456484 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MVVPEKEQSW IPKIFKKKTC TTFIVDSTDP GGTLCQCGRP RTAHPAVAME DAFGAAVVTV WDSDAHTTEK PTDAYGELDF TGAGRKHSN FLRLSDRTDP AAVYSLVTRT WGFRAPNLVV SVLGGSGGPV LQTWLQDLLR RGLVRAAQST GAWIVTGGLH T GIGRHVGV ...String:
MVVPEKEQSW IPKIFKKKTC TTFIVDSTDP GGTLCQCGRP RTAHPAVAME DAFGAAVVTV WDSDAHTTEK PTDAYGELDF TGAGRKHSN FLRLSDRTDP AAVYSLVTRT WGFRAPNLVV SVLGGSGGPV LQTWLQDLLR RGLVRAAQST GAWIVTGGLH T GIGRHVGV AVRDHQMAST GGTKVVAMGV APWGVVRNRD TLINPKGSFP ARYRWRGDPE DGVQFPLDYN YSAFFLVDDG TH GCLGGEN RFRLRLESYI SQQKTGVGGT GIDIPVLLLL IDGDEKMLTR IENATQAQLP CLLVAGSGGA ADCLAETLED TLA PGSGGA RQGEARDRIR RFFPKGDLEV LQAQVERIMT RKELLTVYSS EDGSEEFETI VLKALVKACG SSEASAYLDE LRLA VAWNR VDIAQSELFR GDIQWRSFHL EASLMDALLN DRPEFVRLLI SHGLSLGHFL TPMRLAQLYS AAPSNSLIRN LLDQA SHSA GTKAPALKGG AAELRPPDVG HVLRMLLGKM CAPRYPSGGA WDPHPGQGFG ESMYLLSDKA TSPLSLDAGL GQAPWS DLL LWALLLNRAQ MAMYFWEMGS NAVSSALGAC LLLRVMARLE PDAEEAARRK DLAFKFEGMG VDLFGECYRS SEVRAAR LL LRRCPLWGDA TCLQLAMQAD ARAFFAQDGV QSLLTQKWWG DMASTTPIWA LVLAFFCPPL IYTRLITFRK SEEEPTRE E LEFDMDSVIN GEGPVGTADP AEKTPLGVPR QSGRPGCCGG RCGGRRCLRR WFHFWGAPVT IFMGNVVSYL LFLLLFSRV LLVDFQPAPP GSLELLLYFW AFTLLCEELR QGLSGGGGSL ASGGPGPGHA SLSQRLRLYL ADSWNQCDLV ALTCFLLGVG CRLTPGLYH LGRTVLCIDF MVFTVRLLHI FTVNKQLGPK IVIVSKMMKD VFFFLFFLGV WLVAYGVATE GLLRPRDSDF P SILRRVFY RPYLQIFGQI PQEDMDVALM EHSNCSSEPG FWAHPPGAQA GTCVSQYANW LVVLLLVIFL LVANILLVNL LI AMFSYTF GKVQGNSDLY WKAQRYRLIR EFHSRPALAP PFIVISHLRL LLRQLCRRPR SPQPSSPALE HFRVYLSKEA ERK LLTWES VHKENFLLAR ARDKRESDSE RLKRTSQKVD LALKQLGHIR EYEQRLKVLE REVQQCSRVL GWVAEALSRS ALLP PGGPP PPDLPGSKD

UniProtKB: Transient receptor potential cation channel subfamily M member 4

-
Macromolecule #2: Necrocide 1

MacromoleculeName: Necrocide 1 / type: ligand / ID: 2 / 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
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 40.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.4000000000000001 µm / Nominal defocus min: 0.5 µm

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.58 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 1475055
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

+
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