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- EMDB-71253: Zebrafish TRPM5 D797N mutant with 5mM calcium and 0.5mM CBTA -

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Basic information

Entry
Database: EMDB / ID: EMD-71253
TitleZebrafish TRPM5 D797N mutant with 5mM calcium and 0.5mM CBTA
Map dataZebrafish TRPM5 D797N mutant with 5mM calcium and 0.5mM CBTA
Sample
  • Complex: zebrafish TRPM5 D797N mutant in GDN detergent with 5mM calcium and 0.5mM CBTA
    • Protein or peptide: Transient receptor potential cation channel subfamily M member 5 isoform X1
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CALCIUM ION
  • Ligand: Tigogenin
  • Ligand: 5-chloro-N-[(5-chloro-1,3-thiazol-2-yl)methyl]-1,2-benzothiazol-6-amine
  • Ligand: (2R)-2-(hydroxymethyl)-4-{[(10xi,13xi,22xi,25R)-5beta,14beta,17beta-spirostan-3beta-yl]oxy}butyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside
KeywordsTRPM5 channel / ion channel / cation channel / sodium channel / TRANSPORT PROTEIN
Function / homology
Function and homology information


calcium channel activity / membrane
Similarity search - Function
: / Transient receptor potential channel, canonical / 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 5 isoform X1
Similarity search - Component
Biological speciesDanio rerio (zebrafish)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.27 Å
AuthorsRuan Z / Du J / Lu W
Funding support United States, 6 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)R00NS128258 United States
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)R01NS112363 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35GM138321 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)R01NS129804 United States
CitationJournal: Nat Chem Biol / Year: 2026
Title: A single allosteric site merges activation, modulation and inhibition in TRPM5.
Authors: Zheng Ruan / Junuk Lee / Yangyang Li / Ian J Orozco / Juan Du / Wei Lü /
Abstract: TRPM5 is a Ca-activated monovalent cation channel essential for taste perception, insulin secretion and gastrointestinal chemosensation. Canonical TRPM5 activation requires Ca binding at two distinct ...TRPM5 is a Ca-activated monovalent cation channel essential for taste perception, insulin secretion and gastrointestinal chemosensation. Canonical TRPM5 activation requires Ca binding at two distinct sites: an agonist site within the lower vestibule of the S1-S4 pocket in the transmembrane domain (Ca) and a modulatory site in the intracellular domain (Ca) that tunes voltage dependence and agonist sensitivity. Here we characterize CBTA as a noncalcium agonist that binds to the upper vestibule of the S1-S4 pocket, directly above Ca. CBTA alone mimics the dual role of Ca and Ca, merging agonist activation with voltage modulation. CBTA also renders TRPM5 supersensitive to Ca, synergistically hyperactivating the channel even at near-resting Ca levels. We further demonstrate that the inhibitor triphenylphosphine oxide binds the same site but stabilizes a nonconductive state. These opposing effects reveal the upper S1-S4 pocket as a multifunctional regulatory hub integrating activation, inhibition and modulation in TRPM5.
History
DepositionJun 14, 2025-
Header (metadata) releaseJan 7, 2026-
Map releaseJan 7, 2026-
UpdateJan 21, 2026-
Current statusJan 21, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_71253.png

Downloads & links

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Map

FileDownload / File: emd_71253.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationZebrafish TRPM5 D797N mutant with 5mM calcium and 0.5mM CBTA
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 360 pix.
= 297.36 Å		0.83 Å/pix.
x 360 pix.
= 297.36 Å		0.83 Å/pix.
x 360 pix.
= 297.36 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.826 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.003
Minimum - Maximum-0.005719449 - 0.016350761
Average (Standard dev.)0.00007001348 (±0.0007235153)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 297.36 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_71253_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Additional map: Additional Map

Fileemd_71253_additional_1.map
AnnotationAdditional Map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Half Map B

Fileemd_71253_half_map_1.map
AnnotationHalf Map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Half Map A

Fileemd_71253_half_map_2.map
AnnotationHalf Map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : zebrafish TRPM5 D797N mutant in GDN detergent with 5mM calcium an...

EntireName: zebrafish TRPM5 D797N mutant in GDN detergent with 5mM calcium and 0.5mM CBTA
Components
  • Complex: zebrafish TRPM5 D797N mutant in GDN detergent with 5mM calcium and 0.5mM CBTA
    • Protein or peptide: Transient receptor potential cation channel subfamily M member 5 isoform X1
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CALCIUM ION
  • Ligand: Tigogenin
  • Ligand: 5-chloro-N-[(5-chloro-1,3-thiazol-2-yl)methyl]-1,2-benzothiazol-6-amine
  • Ligand: (2R)-2-(hydroxymethyl)-4-{[(10xi,13xi,22xi,25R)-5beta,14beta,17beta-spirostan-3beta-yl]oxy}butyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside

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Supramolecule #1: zebrafish TRPM5 D797N mutant in GDN detergent with 5mM calcium an...

SupramoleculeName: zebrafish TRPM5 D797N mutant in GDN detergent with 5mM calcium and 0.5mM CBTA
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Danio rerio (zebrafish)

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Macromolecule #1: Transient receptor potential cation channel subfamily M member 5 ...

MacromoleculeName: Transient receptor potential cation channel subfamily M member 5 isoform X1
type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Danio rerio (zebrafish)
Molecular weightTheoretical: 137.517422 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MLGNQDTPLG VLRQGRRCVQ CGELMYESQG YSSLVGCRCY TPLTQSVVSM VEKSSERFDK QMAGRLGDID FTGVSRTRGK FVRVTSSTD PAEIYQILTK QWGLAPPHLV VALMGGDEVA QLKPWLRDTL RKGLVKAAQS TGAWILTSGL RFGITKNLGQ A VRDHSLAS ...String:
MLGNQDTPLG VLRQGRRCVQ CGELMYESQG YSSLVGCRCY TPLTQSVVSM VEKSSERFDK QMAGRLGDID FTGVSRTRGK FVRVTSSTD PAEIYQILTK QWGLAPPHLV VALMGGDEVA QLKPWLRDTL RKGLVKAAQS TGAWILTSGL RFGITKNLGQ A VRDHSLAS TSPKVRVVAI GIAPWNMIQN RDLLLSAKPD HPATYPTEDL PYGAVYSLDC NHSHFILVDE DPKRPGATGE MR VKMLKHI SLQRTGYGGT GSIEIPVLCL LVHGEPRILQ KMYKNIQNSI PWLILAGSGG VADILVTLMD RGCWDADIVQ ELL INTFPD GLHSTEITSW TKLIQRILDH GHLLTVHDPE QDSELDTVIL KALVKACKSQ SQEAQDFLDE LKLAVAWNRV DIAK SEIFS GDVQWSAQDL EEVMMEALVN DKPDFVRLFV DNGVNIKQFL TYGRLQELYC SVSEKNLLHT LLLKKNQERQ AQLAR KRMS GNPNNELGDR KFRFTFHEVS KVLKDFLDDT CKGFYQKLPA VSKALHQKNL PDMDRRCEHP WRDLFLWAIL QNRQEM ANY FWAMGPEAVA AALVGCKIMK EMAHLATEAE SARSMKNAKY EQFAMDLFSE CYSNSEDRAY SLLVRKTCCW SKATVLN IA TLAEAKCFFA HDGVQALLTK VWWGAMRTDT SISRLVLTFF IPPLVWTSLI KFNPEEQVSK DEGEPFAELD SLETEQAL L LTDGDPVAGE GSAETAARSC SATFIRVVLR RWNRFWSAPV TVFMGNVIMY FAFLILFSYV LLLDFRPPPP YGPSAAEII LYFWVFTLVL EEIRQSFFTD EDMSILKKMK LYVEDNWNKC NMVAISLFVV GLSCRMAMST YEAGRTVLAL DFMVFTLRLI HIFAIHKQL GPKIIIVERM IKDVFFFLFF LSVWLIAYGV TTQALLHPND PRIDWVFRRA LYRPYLHIFG QIPLEEIDAA K MPDDNCTT DVQEIILGTL PPCPNIYANW LVILLLVIYL LVTNVLLLNL LIAMFSYTFQ VVQENADIFW KFQRYNLIVE YH SRPALAP PFIIISHITQ ALLSFIKKTE NTQDLLEREL PSGLDQKLMT WETVQKENYL AKLEHEHRES SGERLRYTSS KVQ TLLRMV GGFKDQEKRM ATVETEVRYC GEVLSWIAEC FHKSTLKCDR DAPKAPRSIA GSSRDQQPQG AKRQQPAGHP AYGT DKKLP FIDH

UniProtKB: Transient receptor potential cation channel subfamily M member 5 isoform X1

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Macromolecule #2: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 4 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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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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Macromolecule #4: Tigogenin

MacromoleculeName: Tigogenin / type: ligand / ID: 4 / Number of copies: 4 / Formula: A1CGZ
Molecular weightTheoretical: 416.636 Da

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Macromolecule #5: 5-chloro-N-[(5-chloro-1,3-thiazol-2-yl)methyl]-1,2-benzothiazol-6...

MacromoleculeName: 5-chloro-N-[(5-chloro-1,3-thiazol-2-yl)methyl]-1,2-benzothiazol-6-amine
type: ligand / ID: 5 / Number of copies: 4 / Formula: A1CGW
Molecular weightTheoretical: 316.229 Da

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Macromolecule #6: (2R)-2-(hydroxymethyl)-4-{[(10xi,13xi,22xi,25R)-5beta,14beta,17be...

MacromoleculeName: (2R)-2-(hydroxymethyl)-4-{[(10xi,13xi,22xi,25R)-5beta,14beta,17beta-spirostan-3beta-yl]oxy}butyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside
type: ligand / ID: 6 / Number of copies: 4 / Formula: A1CG0
Molecular weightTheoretical: 843.049 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

BufferpH: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.9000000000000001 µm / Nominal defocus min: 1.1 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.27 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 75674
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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