[English] 日本語
Yorodumi
- PDB-9mtc: Cryo-EM structure of the human TRPM4 channel in a ATP bound inhib... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9mtc
TitleCryo-EM structure of the human TRPM4 channel in a ATP bound inhibited state
ComponentsTransient receptor potential cation channel subfamily M member 4
KeywordsTRANSPORT PROTEIN / TRPM4 / Ion channel
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 / 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 / negative regulation of bone mineralization / 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 / 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 / negative regulation of bone mineralization / 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 / positive regulation of vasoconstriction / cellular response to ATP / monoatomic cation transmembrane transport / regulation of heart rate by cardiac conduction / protein sumoylation / negative regulation of osteoblast differentiation / positive regulation of fat cell differentiation / positive regulation of insulin secretion involved in cellular response to glucose stimulus / positive regulation of heart rate / positive regulation of adipose tissue development / calcium-mediated signaling / calcium ion transmembrane transport / calcium channel activity / Sensory perception of sweet, bitter, and umami (glutamate) taste / positive regulation of canonical Wnt signaling pathway / 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 / endoplasmic reticulum / Golgi apparatus / nucleoplasm / ATP binding / identical protein binding / membrane / plasma membrane
Similarity search - Function
TRPM, SLOG domain / : / SLOG in TRPM / TRPM2-like domain / Ion transport domain / Ion transport protein
Similarity search - Domain/homology
ADENOSINE-5'-TRIPHOSPHATE / Transient receptor potential cation channel subfamily M member 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.63 Å
AuthorsTeixeira-Duarte, C.M. / Jiang, Y.
Funding support United States, 3items
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 Struct Mol Biol / Year: 2025
Title: Structural landscape of activation, desensitization and inhibition in the human TRPM4 channel.
Authors: Celso M Teixeira-Duarte / Weizhong Zeng / Youxing Jiang /
Abstract: TRPM4 is a member of the transient receptor potential melastatin channel subfamily and functions as a Ca-activated monovalent-selective cation channel. It is widely expressed in various cells and ...TRPM4 is a member of the transient receptor potential melastatin channel subfamily and functions as a Ca-activated monovalent-selective cation channel. It is widely expressed in various cells and tissues, where its activation depolarizes the plasma membrane potential and modulates various Ca-dependent biological processes. TRPM4 activity is potentiated by membrane phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P) and inhibited by cytosolic free adenosine triphosphate (ATP), allowing the channel to transition between different functional states in response to dynamic changes in cellular Ca, ATP and PtdIns(4,5)P levels during signaling events. Here we present single-particle cryo-electron microscopy structures of human TRPM4 in four distinct states: apo closed, Ca-bound putative desensitized, Ca-PtdIns(4,5)P-bound open and ATP-bound inhibited. Combined with mutagenesis and electrophysiological analyses, these structures reveal the molecular mechanisms underlying TRPM4 activation, desensitization and inhibition. Given the central roles of Ca, PtdIns(4,5)P and ATP in cellular signaling, this work provides a structural foundation to decipher the physiological functions of TRPM4 across diverse biological systems.
History
DepositionJan 10, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 29, 2025Provider: repository / Type: Initial release
Revision 1.1Nov 12, 2025Group: Data collection / Database references / Category: citation / em_admin
Item: _citation.pdbx_database_id_PubMed / _citation.title / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
B: Transient receptor potential cation channel subfamily M member 4
A: Transient receptor potential cation channel subfamily M member 4
C: Transient receptor potential cation channel subfamily M member 4
D: Transient receptor potential cation channel subfamily M member 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)539,8558
Polymers537,8264
Non-polymers2,0294
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

#1: Protein
Transient receptor potential cation channel subfamily M member 4 / hTRPM4 / Calcium-activated non-selective cation channel 1 / Long transient receptor potential ...hTRPM4 / Calcium-activated non-selective cation channel 1 / Long transient receptor potential channel 4 / LTrpC4 / Melastatin-4


Mass: 134456.484 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TRPM4, LTRPC4 / Production host: Homo sapiens (human) / References: UniProt: Q8TD43
#2: Chemical
ChemComp-ATP / ADENOSINE-5'-TRIPHOSPHATE


Mass: 507.181 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C10H16N5O13P3 / Feature type: SUBJECT OF INVESTIGATION / Comment: ATP, energy-carrying molecule*YM
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: human TRPM4 / Type: COMPLEX / Entity ID: #1 / Source: NATURAL
Source (natural)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 900 nm
Image recordingElectron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

EM softwareName: PHENIX / Version: 1.21.2_5419 / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.63 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 153652 / Symmetry type: POINT
RefinementCross valid method: NONE

+
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