[English] 日本語
Yorodumi
- PDB-9isg: Structure of rat TRPV1 in complex with PSFL426-S5 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9isg
TitleStructure of rat TRPV1 in complex with PSFL426-S5
ComponentsTransient receptor potential cation channel subfamily V member 1
KeywordsMEMBRANE PROTEIN / TRPV1 / protein complex
Function / homology
Function and homology information


peptide secretion / negative regulation of iodide transmembrane transport / detection of temperature stimulus involved in thermoception / sensory perception of mechanical stimulus / negative regulation of establishment of blood-brain barrier / positive regulation of membrane depolarization / positive regulation of renal sodium excretion / response to capsazepine / cellular response to temperature stimulus / detection of chemical stimulus involved in sensory perception of pain ...peptide secretion / negative regulation of iodide transmembrane transport / detection of temperature stimulus involved in thermoception / sensory perception of mechanical stimulus / negative regulation of establishment of blood-brain barrier / positive regulation of membrane depolarization / positive regulation of renal sodium excretion / response to capsazepine / cellular response to temperature stimulus / detection of chemical stimulus involved in sensory perception of pain / positive regulation of sensory perception of pain / temperature-gated ion channel activity / smooth muscle contraction involved in micturition / fever generation / negative regulation of axon regeneration / diet induced thermogenesis / TRP channels / positive regulation of cardiac muscle cell differentiation / urinary bladder smooth muscle contraction / thermoception / glutamate secretion / response to pH / monoatomic cation transmembrane transporter activity / response to pain / response to acidic pH / negative regulation of systemic arterial blood pressure / excitatory extracellular ligand-gated monoatomic ion channel activity / dendritic spine membrane / positive regulation of urine volume / negative regulation of heart rate / cellular response to alkaloid / sensory perception of taste / cellular response to cytokine stimulus / temperature homeostasis / intracellularly gated calcium channel activity / cellular response to ATP / behavioral response to pain / detection of temperature stimulus involved in sensory perception of pain / negative regulation of mitochondrial membrane potential / calcium ion import across plasma membrane / positive regulation of vasoconstriction / monoatomic ion channel activity / ligand-gated monoatomic ion channel activity / monoatomic cation channel activity / cellular response to acidic pH / extracellular ligand-gated monoatomic ion channel activity / sensory perception of pain / phosphatidylinositol binding / axon terminus / positive regulation of excitatory postsynaptic potential / lipid metabolic process / sarcoplasmic reticulum / cellular response to tumor necrosis factor / phosphoprotein binding / microglial cell activation / cellular response to nerve growth factor stimulus / cellular response to growth factor stimulus / response to peptide hormone / GABA-ergic synapse / positive regulation of nitric oxide biosynthetic process / calcium ion transmembrane transport / calcium channel activity / calcium ion transport / transmembrane signaling receptor activity / cellular response to heat / response to heat / positive regulation of cytosolic calcium ion concentration / monoatomic ion transmembrane transport / protein homotetramerization / calmodulin binding / postsynaptic membrane / neuron projection / positive regulation of apoptotic process / external side of plasma membrane / neuronal cell body / dendrite / negative regulation of transcription by RNA polymerase II / ATP binding / membrane / metal ion binding / identical protein binding / nucleus / plasma membrane
Similarity search - Function
Transient receptor potential cation channel subfamily V member 1-4 / Transient receptor potential cation channel subfamily V / Ankyrin repeat / Ankyrin repeat profile. / Ankyrin repeats (3 copies) / Ankyrin repeat region circular profile. / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily / Ion transport domain / Ion transport protein
Similarity search - Domain/homology
: / Transient receptor potential cation channel subfamily V member 1
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å
AuthorsChen, X. / Yu, Y.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32371289 China
CitationJournal: Nat Chem Biol / Year: 2025
Title: Mechanism of capsaicin entry into buried vanilloid sites in TRPV1.
Authors: Meng-Yang Sun / Yu-Jing Bian / Xiao-Ying Chen / Xue Zhang / Ming Li / Bo-Ying Zhou / Yang Yang / Yi-Zhe Huang / Rui Yang / Yu-Hao Gao / Wen-Wen Cui / Ya-Qi Wang / Si-Jia Zhu / Peng Cao / ...Authors: Meng-Yang Sun / Yu-Jing Bian / Xiao-Ying Chen / Xue Zhang / Ming Li / Bo-Ying Zhou / Yang Yang / Yi-Zhe Huang / Rui Yang / Yu-Hao Gao / Wen-Wen Cui / Ya-Qi Wang / Si-Jia Zhu / Peng Cao / Chang-Zhu Li / Michael X Zhu / Yun-Tao Lei / Fan Yang / Ye Yu /
Abstract: The transient receptor potential vanilloid 1 (TRPV1) receptor is a promising target for nonopioid analgesics, yet hyperthermic side effects have hindered drug development. The prevailing perspective ...The transient receptor potential vanilloid 1 (TRPV1) receptor is a promising target for nonopioid analgesics, yet hyperthermic side effects have hindered drug development. The prevailing perspective maintains that extracellular hydrophobic vanilloid ligands, such as capsaicin, traverse the cell membrane to reach the buried vanilloid site during TRPV1 activation. Here, we present an alternative mechanism based on computational and experimental approaches, which suggests a distinct hydrophobic pathway at the TRPV1-cell membrane interface as the principal route for ligand entry to the vanilloid site, rather than direct membrane penetration. Modifications to residues within this pathway greatly delayed capsaicin entry without directly modulating TRPV1 channel gating. A compound designed to occupy this pathway's entrance exhibited analgesic effects without inducing hyperthermia. Cryo-electron microscopy confirmed binding to TRPV1 and its role in perturbing capsaicin entry. Thus, our findings unveil a unique and targetable route for capsaicin access to the TRPV1 vanilloid site.
History
DepositionJul 17, 2024Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Jul 23, 2025Provider: repository / Type: Initial release
Revision 1.0Jul 23, 2025Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Jul 23, 2025Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Jul 23, 2025Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 23, 2025Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 23, 2025Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Jul 23, 2025Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Aug 13, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _em_admin.last_update
Revision 1.2Dec 10, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Transient receptor potential cation channel subfamily V member 1
B: Transient receptor potential cation channel subfamily V member 1
C: Transient receptor potential cation channel subfamily V member 1
D: Transient receptor potential cation channel subfamily V member 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)399,2168
Polymers398,5834
Non-polymers6334
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

#1: Protein
Transient receptor potential cation channel subfamily V member 1 / TrpV1 / Capsaicin receptor / Osm-9-like TRP channel 1 / OTRPC1 / Vanilloid receptor 1 / Vanilloid ...TrpV1 / Capsaicin receptor / Osm-9-like TRP channel 1 / OTRPC1 / Vanilloid receptor 1 / Vanilloid receptor type 1-like


Mass: 99645.812 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Trpv1, Vr1, Vr1l / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: O35433
#2: Chemical
ChemComp-A1D92 / 4-azanyl-3-sulfanylidene-1,2,4-triazine-5,6-dione


Mass: 158.139 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C3H2N4O2S
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: Structure of rat TRPV1 in complex with PSFL426-S5 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Source (natural)Organism: Rattus norvegicus (Norway rat)
Source (recombinant)Organism: Homo sapiens (human) / Cell: HEK293
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1600 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm
Image recordingAverage exposure time: 4.5 sec. / Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

-
Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 15808 / Symmetry type: POINT

+
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