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- EMDB-63651: Structure of human TRPC5 bound with (-)-englerin A,class1 -

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Basic information

Entry
Database: EMDB / ID: EMD-63651
TitleStructure of human TRPC5 bound with (-)-englerin A,class1
Map dataSharpened map
Sample
  • Complex: human TRPC5
    • Protein or peptide: Short transient receptor potential channel 5
  • Ligand: CHOLESTEROL HEMISUCCINATE
  • Ligand: ZINC ION
  • Ligand: CALCIUM ION
  • Ligand: PHOSPHATIDYLETHANOLAMINE
  • Ligand: (-)-englerin A
KeywordsTRPC5 / ion channel / (-)-englerin A / cryo-EM / MEMBRANE PROTEIN
Function / homology
Function and homology information


regulation of membrane hyperpolarization / phosphatidylserine exposure on apoptotic cell surface / negative regulation of dendrite morphogenesis / Role of second messengers in netrin-1 signaling / store-operated calcium channel activity / inositol 1,4,5 trisphosphate binding / cation channel complex / actinin binding / clathrin binding / TRP channels ...regulation of membrane hyperpolarization / phosphatidylserine exposure on apoptotic cell surface / negative regulation of dendrite morphogenesis / Role of second messengers in netrin-1 signaling / store-operated calcium channel activity / inositol 1,4,5 trisphosphate binding / cation channel complex / actinin binding / clathrin binding / TRP channels / regulation of cytosolic calcium ion concentration / positive regulation of axon extension / calcium channel complex / positive regulation of neuron differentiation / calcium ion transmembrane transport / calcium channel activity / neuron differentiation / calcium ion transport / nervous system development / presynapse / positive regulation of cytosolic calcium ion concentration / growth cone / ATPase binding / actin binding / neuron apoptotic process / neuronal cell body / positive regulation of cell population proliferation / dendrite / plasma membrane
Similarity search - Function
Transient receptor potential channel, canonical 5 / Transient receptor ion channel domain / Transient receptor ion channel II / Transient receptor ion channel II / Transient receptor potential channel, canonical / Ankyrin repeat / Ankyrin repeats (3 copies) / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily ...Transient receptor potential channel, canonical 5 / Transient receptor ion channel domain / Transient receptor ion channel II / Transient receptor ion channel II / Transient receptor potential channel, canonical / Ankyrin repeat / Ankyrin repeats (3 copies) / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily / Ion transport domain / Ion transport protein
Similarity search - Domain/homology
Short transient receptor potential channel 5
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.53 Å
AuthorsChen YK / Wei M / Chen L / Guo WJ
Funding support China, 2 items
OrganizationGrant numberCountry
Ministry of Science and Technology (MoST, China)2022YFA0806504 China
National Natural Science Foundation of China (NSFC)32225027 China
CitationJournal: Protein Sci / Year: 2025
Title: Mechanism of (-)-Englerin A and calcium binding on the human TRPC5 channel.
Authors: Yikun Chen / Kangcheng Song / Wenjun Guo / Miao Wei / Lei Chen /
Abstract: The natural product (-)-Englerin A (EA) selectively inhibits renal cancer cell growth by potently activating TRPC4 and TRPC5-containing ion channels. However, its binding site on these channels has ...The natural product (-)-Englerin A (EA) selectively inhibits renal cancer cell growth by potently activating TRPC4 and TRPC5-containing ion channels. However, its binding site on these channels has remained elusive. In this study, we present two cryo-EM structures of human TRPC5 in complex with EA at 2.5 and 2.6 Å resolution, which reveal the EA-binding site and identify two major conformations influenced by calcium. EA binds between the pore helix and S5/S6 helices of hTRPC5, forming critical hydrophobic and polar interactions that underscore its specificity. Calcium binding at the intracellular domain of TRPC5 induces structural changes that stabilize the domain in a compact conformation. These findings expand our understanding of the structural pharmacology of TRPC5 and provide a framework for investigating calcium regulation in TRPC channels.
History
DepositionMar 6, 2025-
Header (metadata) releaseJul 2, 2025-
Map releaseJul 2, 2025-
UpdateNov 12, 2025-
Current statusNov 12, 2025Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_63651.png

Downloads & links

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Map

FileDownload / File: emd_63651.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationSharpened map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.04 Å/pix.
x 320 pix.
= 333.12 Å		1.04 Å/pix.
x 320 pix.
= 333.12 Å		1.04 Å/pix.
x 320 pix.
= 333.12 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.041 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.6
Minimum - Maximum-4.5033607 - 6.5989065
Average (Standard dev.)-0.0017473692 (±0.14950548)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 333.12 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: Half map

Fileemd_63651_half_map_1.map
AnnotationHalf map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Half map

Fileemd_63651_half_map_2.map
AnnotationHalf map
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 TRPC5

EntireName: human TRPC5
Components
  • Complex: human TRPC5
    • Protein or peptide: Short transient receptor potential channel 5
  • Ligand: CHOLESTEROL HEMISUCCINATE
  • Ligand: ZINC ION
  • Ligand: CALCIUM ION
  • Ligand: PHOSPHATIDYLETHANOLAMINE
  • Ligand: (-)-englerin A

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Supramolecule #1: human TRPC5

SupramoleculeName: human TRPC5 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Short transient receptor potential channel 5

MacromoleculeName: Short transient receptor potential channel 5 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 111.916414 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: PEFMAQLYYK KVNYSPYRDR IPLQIVRAET ELSAEEKAFL NAVEKGDYAT VKQALQEAEI YYNVNINCMD PLGRSALLIA IENENLEIM ELLLNHSVYV GDALLYAIRK EVVGAVELLL SYRRPSGEKQ VPTLMMDTQF SEFTPDITPI MLAAHTNNYE I IKLLVQKR ...String:
PEFMAQLYYK KVNYSPYRDR IPLQIVRAET ELSAEEKAFL NAVEKGDYAT VKQALQEAEI YYNVNINCMD PLGRSALLIA IENENLEIM ELLLNHSVYV GDALLYAIRK EVVGAVELLL SYRRPSGEKQ VPTLMMDTQF SEFTPDITPI MLAAHTNNYE I IKLLVQKR VTIPRPHQIR CNCVECVSSS EVDSLRHSRS RLNIYKALAS PSLIALSSED PILTAFRLGW ELKELSKVEN EF KAEYEEL SQQCKLFAKD LLDQARSSRE LEIILNHRDD HSEELDPQKY HDLAKLKVAI KYHQKEFVAQ PNCQQLLATL WYD GFPGWR RKHWVVKLLT CMTIGFLFPM LSIAYLISPR SNLGLFIKKP FIKFICHTAS YLTFLFMLLL ASQHIVRTDL HVQG PPPTV VEWMILPWVL GFIWGEIKEM WDGGFTEYIH DWWNLMDFAM NSLYLATISL KIVAYVKYNG SRPREEWEMW HPTLI AEAL FAISNILSSL RLISLFTANS HLGPLQISLG RMLLDILKFL FIYCLVLLAF ANGLNQLYFY YETRAIDEPN NCKGIR CEK QNNAFSTLFE TLQSLFWSVF GLLNLYVTNV KARHEFTEFV GATMFGTYNV ISLVVLLNML IAMMNNSYQL IADHADI EW KFARTKLWMS YFDEGGTLPP PFNIIPSPKS FLYLGNWFNN TFCPKRDPDG RRRRRNLRSF TERNADSLIQ NQHYQEVI R NLVKRYVAAM IRNSKTHEGL TEENFKELKQ DISSFRYEVL DLLGNRKHPR SFSTSSTELS QRDDNNDGSG GARAKSKSV SFNLGCKKKT CHGPPLIRTM PRSSGAQGKS KAESSSKRSF MGPSLKKLGL LFSKFNGHMS EPSSEPMYTI SDGIVQQHCM WQDIRYSQM EKGKAEACSQ SEINLSEVEL GEVQGAAQSS ECPLACSSSL HCASSICSSN SKLLDSSEDV FETWGEACDL L MHKWGDGQ EEQVTTRL

UniProtKB: Short transient receptor potential channel 5

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Macromolecule #2: CHOLESTEROL HEMISUCCINATE

MacromoleculeName: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 2 / Number of copies: 4 / Formula: Y01
Molecular weightTheoretical: 486.726 Da
Chemical component information

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

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Macromolecule #3: ZINC ION

MacromoleculeName: ZINC ION / type: ligand / ID: 3 / Number of copies: 4 / Formula: ZN
Molecular weightTheoretical: 65.409 Da

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Macromolecule #4: CALCIUM ION

MacromoleculeName: CALCIUM ION / type: ligand / ID: 4 / Number of copies: 4 / Formula: CA
Molecular weightTheoretical: 40.078 Da

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Macromolecule #5: PHOSPHATIDYLETHANOLAMINE

MacromoleculeName: PHOSPHATIDYLETHANOLAMINE / type: ligand / ID: 5 / Number of copies: 4 / Formula: PTY
Molecular weightTheoretical: 734.039 Da
Chemical component information

ChemComp-PTY:
PHOSPHATIDYLETHANOLAMINE / phospholipid*YM

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Macromolecule #6: (-)-englerin A

MacromoleculeName: (-)-englerin A / type: ligand / ID: 6 / Number of copies: 4 / Formula: A1L55
Molecular weightTheoretical: 442.545 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: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Number real images: 1311 / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 1.5 µm
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: 2.53 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 145349
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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