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- EMDB-52611: Human TRPM4 ion channel in MAASTY copolymer lipid nanodisc in a c... -

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Basic information

Entry
Database: EMDB / ID: EMD-52611
TitleHuman TRPM4 ion channel in MAASTY copolymer lipid nanodisc in a calcium-bound state
Map dataSharpened EM density map of hTRPM4 in MAASTY lipid nanodiscs.
Sample
  • Complex: Human TRPM4 transient receptor potential cation channel subfamily M member 4 from Homo sapiens
    • Protein or peptide: Transient receptor potential cation channel subfamily M member 4
  • Ligand: CHOLESTEROL
  • Ligand: CALCIUM ION
KeywordsIon Channel / Copolymer / Native Nanodisc / Calcium-bound / 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 / 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 / cellular response to ATP / positive regulation of vasoconstriction / sodium channel activity / 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
Transient receptor potential cation channel subfamily M member 4
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.46 Å
AuthorsPugh CF / Feilen LP / Zivkovic D / Praestegaard KF / Sideris C / Borthwick NJ / De Lichtenberg C / Bolla JR / Autzen AAA / Autzen HE
Funding support Denmark, 1 items
OrganizationGrant numberCountry
Novo Nordisk Foundation Denmark
CitationJournal: Nat Commun / Year: 2025
Title: MAASTY: a (dis)ordered copolymer for structural determination of human membrane proteins in native nanodiscs.
Authors: Ciara F Pugh / Lukas P Feilen / Dušan Živković / Kaia F Præstegaard / Charalampos Sideris / Neil J Borthwick / Casper de Lichtenberg / Jani R Bolla / Anton A A Autzen / Henriette E Autzen /
Abstract: Amphiphilic copolymers capable of extracting membrane proteins directly from cellular membranes into "native nanodiscs" offer a simplified approach for preparing membrane proteins in lipid nanodiscs ...Amphiphilic copolymers capable of extracting membrane proteins directly from cellular membranes into "native nanodiscs" offer a simplified approach for preparing membrane proteins in lipid nanodiscs compared to approaches that rely on detergent. Copolymer amphiphilicity, length, and composition influence their performance, in addition to the protein itself and the purification conditions used. Here, we report a copolymer composed of methacrylic acid and styrene, which we term MAASTY, leveraging the inherent monomer reactivity ratios to create an anionic copolymer with a statistical distribution of monomers. We show that MAASTY can be used for high-resolution structural determination of a human membrane protein by single particle cryo-electron microscopy, preserving endogenous lipids including cholesterol and exhibiting an enrichment of phosphatidylinositol. Moreover, MAASTY copolymers effectively solubilize a broad range of lipid species and a wide range of different, eukaryotic membrane proteins from mammalian cells. We find that MAASTY copolymers are promising as effective solubilizers of membrane proteins and offer a chemical platform for structural and functional characterization of membrane proteins in native nanodiscs.
History
DepositionJan 23, 2025-
Header (metadata) releaseJan 28, 2026-
Map releaseJan 28, 2026-
UpdateJan 28, 2026-
Current statusJan 28, 2026Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_52611.png

Downloads & links

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Map

FileDownload / File: emd_52611.map.gz / Format: CCP4 / Size: 343 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationSharpened EM density map of hTRPM4 in MAASTY lipid nanodiscs.
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.73 Å/pix.
x 448 pix.
= 324.8 Å		0.73 Å/pix.
x 448 pix.
= 324.8 Å		0.73 Å/pix.
x 448 pix.
= 324.8 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.725 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0045
Minimum - Maximum-0.038132362 - 0.056238163
Average (Standard dev.)0.000109049935 (±0.0012377935)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions448448448
Spacing448448448
CellA=B=C: 324.80002 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_52611_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Additional map: Unsharpened EM density map of hTRPM4 in MAASTY lipid nanodiscs.

Fileemd_52611_additional_1.map
AnnotationUnsharpened EM density map of hTRPM4 in MAASTY lipid nanodiscs.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: EM density half map 2 from EM density...

Fileemd_52611_half_map_1.map
AnnotationEM density half map 2 from EM density map of hTRPM4 in MAASTY lipid nanodiscs.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: EM density half map 1 from EM density...

Fileemd_52611_half_map_2.map
AnnotationEM density half map 1 from EM density map of hTRPM4 in MAASTY lipid nanodiscs.
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 transient receptor potential cation channel subfamily...

EntireName: Human TRPM4 transient receptor potential cation channel subfamily M member 4 from Homo sapiens
Components
  • Complex: Human TRPM4 transient receptor potential cation channel subfamily M member 4 from Homo sapiens
    • Protein or peptide: Transient receptor potential cation channel subfamily M member 4
  • Ligand: CHOLESTEROL
  • Ligand: CALCIUM ION

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Supramolecule #1: Human TRPM4 transient receptor potential cation channel subfamily...

SupramoleculeName: Human TRPM4 transient receptor potential cation channel subfamily M member 4 from Homo sapiens
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 537.2 KDa

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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: StrepTagII and eGFP fusion proteins in the N-terminus
Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 134.770734 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: SGRSGVVPEK EQSWIPKIFK KKTCTTFIVD STDPGGTLCQ CGRPRTAHPA VAMEDAFGAA VVTVWDSDAH TTEKPTDAYG ELDFTGAGR KHSNFLRLSD RTDPAAVYSL VTRTWGFRAP NLVVSVLGGS GGPVLQTWLQ DLLRRGLVRA AQSTGAWIVT G GLHTGIGR ...String:
SGRSGVVPEK EQSWIPKIFK KKTCTTFIVD STDPGGTLCQ CGRPRTAHPA VAMEDAFGAA VVTVWDSDAH TTEKPTDAYG ELDFTGAGR KHSNFLRLSD RTDPAAVYSL VTRTWGFRAP NLVVSVLGGS GGPVLQTWLQ DLLRRGLVRA AQSTGAWIVT G GLHTGIGR HVGVAVRDHQ MASTGGTKVV AMGVAPWGVV RNRDTLINPK GSFPARYRWR GDPEDGVQFP LDYNYSAFFL VD DGTHGCL GGENRFRLRL ESYISQQKTG VGGTGIDIPV LLLLIDGDEK MLTRIENATQ AQLPCLLVAG SGGAADCLAE TLE DTLAPG SGGARQGEAR DRIRRFFPKG DLEVLQAQVE RIMTRKELLT VYSSEDGSEE FETIVLKALV KACGSSEASA YLDE LRLAV AWNRVDIAQS ELFRGDIQWR SFHLEASLMD ALLNDRPEFV RLLISHGLSL GHFLTPMRLA QLYSAAPSNS LIRNL LDQA SHSAGTKAPA LKGGAAELRP PDVGHVLRML LGKMCAPRYP SGGAWDPHPG QGFGESMYLL SDKATSPLSL DAGLGQ APW SDLLLWALLL NRAQMAMYFW EMGSNAVSSA LGACLLLRVM ARLEPDAEEA ARRKDLAFKF EGMGVDLFGE CYRSSEV RA ARLLLRRCPL WGDATCLQLA MQADARAFFA QDGVQSLLTQ KWWGDMASTT PIWALVLAFF CPPLIYTRLI TFRKSEEE P TREELEFDMD SVINGEGPVG TADPAEKTPL GVPRQSGRPG CCGGRCGGRR CLRRWFHFWG APVTIFMGNV VSYLLFLLL FSRVLLVDFQ PAPPGSLELL LYFWAFTLLC EELRQGLSGG GGSLASGGPG PGHASLSQRL RLYLADSWNQ CDLVALTCFL LGVGCRLTP GLYHLGRTVL CIDFMVFTVR LLHIFTVNKQ LGPKIVIVSK MMKDVFFFLF FLGVWLVAYG VATEGLLRPR D SDFPSILR RVFYRPYLQI FGQIPQEDMD VALMEHSNCS SEPGFWAHPP GAQAGTCVSQ YANWLVVLLL VIFLLVANIL LV NLLIAMF SYTFGKVQGN SDLYWKAQRY RLIREFHSRP ALAPPFIVIS HLRLLLRQLC RRPRSPQPSS PALEHFRVYL SKE AERKLL TWESVHKENF LLARARDKRE SDSERLKRTS QKVDLALKQL GHIREYEQRL KVLEREVQQC SRVLGWVAEA LSRS ALLPP GGPPPPDLPG SKD

UniProtKB: Transient receptor potential cation channel subfamily M member 4

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Macromolecule #2: CHOLESTEROL

MacromoleculeName: CHOLESTEROL / type: ligand / ID: 2 / Number of copies: 12 / Formula: CLR
Molecular weightTheoretical: 386.654 Da
Chemical component information

ChemComp-CLR:
CHOLESTEROL

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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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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration1.4 mg/mL
BufferpH: 7.4
GridModel: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS KRIOS
Specialist opticsEnergy filter - Name: TFS Selectris X
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 6308 / Average electron dose: 52.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: OTHER / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 165000
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: NONE
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.46 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 5.0) / Number images used: 87697
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software: (Name: cryoSPARC (ver. 4.4.0), RELION (ver. 5.0))
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 5.0)
FSC plot (resolution estimation)

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Atomic model buiding 1

RefinementOverall B value: 92
Output model

PDB-9i3r:
Human TRPM4 ion channel in MAASTY copolymer lipid nanodisc in a calcium-bound state

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