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- PDB-9z21: Cryo-EM structure of human TRPM4 channel in complex with calcium ... -

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Basic information

Entry
Database: PDB / ID: 9z21
TitleCryo-EM structure of human TRPM4 channel in complex with calcium and NC1 at 37 degrees Celsius (consensus)
ComponentsTransient receptor potential cation channel subfamily M member 4
KeywordsMEMBRANE PROTEIN / ion channel / TRP 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 / negative regulation of bone mineralization / 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 / membrane depolarization during AV node cell action potential / membrane depolarization during bundle of His cell action potential / negative regulation of bone mineralization / 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 / protein sumoylation / positive regulation of vasoconstriction / negative regulation of osteoblast differentiation / positive regulation of fat cell 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 / 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 / calcium ion binding / positive regulation of cell population proliferation / endoplasmic reticulum / Golgi apparatus / nucleoplasm / 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)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.83 Å
AuthorsHu, J. / Lu, W. / Du, J.
Funding support United States, 9items
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: To Be Published
Title: Temperature and intrinsic Ca2+ reshape TRPM4 pharmacology
Authors: Jinhong, H. / Sofia, I. / Sung Jin, P. / Junuk, L. / Jennifer, C. / Garrett, O. / Jiangnan, S. / Juan, D. / Wei, L.
History
DepositionNov 4, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 10, 2026Provider: repository / Type: Initial release
Revision 1.0Jun 10, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Jun 10, 2026Data content type: Additional map / Part number: 1 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0Jun 10, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jun 10, 2026Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jun 10, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Jun 10, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Transient receptor potential cation channel subfamily M member 4
B: 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)539,60816
Polymers537,8264
Non-polymers1,78212
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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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-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: Ca / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-A1CY8 / Necrocide 1 / (3S)-3-cycloheptyl-3-(4-hydroxyphenyl)-6-methoxy-7-methyl-1,3-dihydro-2H-indol-2-one


Mass: 365.465 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C23H27NO3 / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

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

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Sample preparation

ComponentName: human TRPM4 channel in complex with calcium and NC1 at 37 degrees Celsius
Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

MicroscopyModel: TFS GLACIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1400 nm / Nominal defocus min: 500 nm
Image recordingElectron dose: 40 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

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Processing

EM software
IDNameCategory
1cryoSPARCparticle selection
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.83 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1635562 / Symmetry type: POINT
RefinementHighest resolution: 2.83 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00431000
ELECTRON MICROSCOPYf_angle_d0.46542184
ELECTRON MICROSCOPYf_dihedral_angle_d9.85310864
ELECTRON MICROSCOPYf_chiral_restr0.0344828
ELECTRON MICROSCOPYf_plane_restr0.0045360

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