[English] 日本語
Yorodumi
- EMDB-63631: Structure of human TRPC5 bound with (-)-englerin A, class 2. -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-63631
TitleStructure of human TRPC5 bound with (-)-englerin A, class 2.
Map dataSharpened map of hTRPC5 with (-)-englerin A in the low calcium.
Sample
  • Complex: human TRPC5
    • Protein or peptide: Short transient receptor potential channel 5
  • Ligand: ZINC ION
  • Ligand: PHOSPHATIDYLETHANOLAMINE
  • Ligand: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
  • Ligand: CHOLESTEROL HEMISUCCINATE
  • Ligand: (-)-englerin A
KeywordsTRPC5 / ion channel / (-)-englerin A / 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: 2.62 Å
AuthorsChen YK / Wei M / Chen L
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 5, 2025-
Header (metadata) releaseJul 2, 2025-
Map releaseJul 2, 2025-
UpdateNov 12, 2025-
Current statusNov 12, 2025Processing site: PDBc / Status: Released

-
Structure visualization

Supplemental images

emd_63631.png

Downloads & links

-
Map

FileDownload / File: emd_63631.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationSharpened map of hTRPC5 with (-)-englerin A in the low calcium.
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.04 Å/pix.
x 320 pix.
= 333.216 Å		1.04 Å/pix.
x 320 pix.
= 333.216 Å		1.04 Å/pix.
x 320 pix.
= 333.216 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.0413 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 1.06
Minimum - Maximum-3.7756226 - 6.1681075
Average (Standard dev.)-0.0017197893 (±0.13121408)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 333.216 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Additional map: Map of hTRPC5 with (-)-englerin A in the low calcium.

Fileemd_63631_additional_1.map
AnnotationMap of hTRPC5 with (-)-englerin A in the low calcium.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Half map of hTRPC5 with (-)-englerin A in the low calcium.

Fileemd_63631_half_map_1.map
AnnotationHalf map of hTRPC5 with (-)-englerin A in the low calcium.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Half map of hTRPC5 with (-)-englerin A in the low calcium.

Fileemd_63631_half_map_2.map
AnnotationHalf map of hTRPC5 with (-)-englerin A in the low calcium.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : human TRPC5

EntireName: human TRPC5
Components
  • Complex: human TRPC5
    • Protein or peptide: Short transient receptor potential channel 5
  • Ligand: ZINC ION
  • Ligand: PHOSPHATIDYLETHANOLAMINE
  • Ligand: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
  • Ligand: CHOLESTEROL HEMISUCCINATE
  • Ligand: (-)-englerin A

-
Supramolecule #1: human TRPC5

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

-
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: 89.221984 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 DLLGNR

UniProtKB: Short transient receptor potential channel 5

-
Macromolecule #2: ZINC ION

MacromoleculeName: ZINC ION / type: ligand / ID: 2 / Number of copies: 4 / Formula: ZN
Molecular weightTheoretical: 65.409 Da

-
Macromolecule #3: PHOSPHATIDYLETHANOLAMINE

MacromoleculeName: PHOSPHATIDYLETHANOLAMINE / type: ligand / ID: 3 / Number of copies: 4 / Formula: PTY
Molecular weightTheoretical: 734.039 Da
Chemical component information

ChemComp-PTY:
PHOSPHATIDYLETHANOLAMINE / phospholipid*YM

-
Macromolecule #4: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...

MacromoleculeName: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
type: ligand / ID: 4 / Number of copies: 4 / Formula: POV
Molecular weightTheoretical: 760.076 Da
Chemical component information

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM

-
Macromolecule #5: CHOLESTEROL HEMISUCCINATE

MacromoleculeName: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 5 / Number of copies: 4 / Formula: Y01
Molecular weightTheoretical: 486.726 Da
Chemical component information

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

-
Macromolecule #6: (-)-englerin A

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

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
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

+
Image processing

CTF correctionType: NONE
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.62 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 109774
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

+
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