[English] 日本語
Yorodumi
- PDB-6puu: Human TRPM2 bound to 8-Br-cADPR and calcium -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6puu
TitleHuman TRPM2 bound to 8-Br-cADPR and calcium
ComponentsTransient receptor potential cation channel subfamily M member 2
KeywordsTRANSPORT PROTEIN / TRPM2 channel / 8-Br-cADPR / calcium
Function / homology
Function and homology information


cellular response to purine-containing compound / mono-ADP-D-ribose binding / manganese ion transmembrane transporter activity / zinc ion transmembrane transport / dendritic cell differentiation / ligand-gated calcium channel activity / response to purine-containing compound / cellular response to temperature stimulus / regulation of filopodium assembly / sodium channel activity ...cellular response to purine-containing compound / mono-ADP-D-ribose binding / manganese ion transmembrane transporter activity / zinc ion transmembrane transport / dendritic cell differentiation / ligand-gated calcium channel activity / response to purine-containing compound / cellular response to temperature stimulus / regulation of filopodium assembly / sodium channel activity / TRP channels / response to hydroperoxide / dendritic cell chemotaxis / calcium ion transmembrane import into cytosol / temperature homeostasis / intracellularly gated calcium channel activity / calcium ion import across plasma membrane / tertiary granule membrane / ficolin-1-rich granule membrane / calcium-mediated signaling using intracellular calcium source / specific granule membrane / monoatomic cation channel activity / release of sequestered calcium ion into cytosol / cellular response to calcium ion / cell projection / calcium ion transmembrane transport / regulation of actin cytoskeleton organization / calcium channel activity / cytoplasmic vesicle membrane / cellular response to hydrogen peroxide / calcium ion transport / response to heat / perikaryon / protein homotetramerization / lysosome / lysosomal membrane / calcium ion binding / Neutrophil degranulation / plasma membrane
Similarity search - Function
TRPM, SLOG domain / SLOG in TRPM / Nudix hydrolase domain profile. / NUDIX hydrolase domain / NUDIX hydrolase-like domain superfamily / Ion transport domain / Ion transport protein
Similarity search - Domain/homology
Chem-CV1 / Transient receptor potential cation channel subfamily M member 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.7 Å
AuthorsDu, J. / Lu, W. / Huang, Y.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)R01NS111031 United States
CitationJournal: Elife / Year: 2019
Title: Ligand recognition and gating mechanism through three ligand-binding sites of human TRPM2 channel.
Authors: Yihe Huang / Becca Roth / Wei Lü / Juan Du /
Abstract: TRPM2 is critically involved in diverse physiological processes including core temperature sensing, apoptosis, and immune response. TRPM2's activation by Ca and ADP ribose (ADPR), an NAD-metabolite ...TRPM2 is critically involved in diverse physiological processes including core temperature sensing, apoptosis, and immune response. TRPM2's activation by Ca and ADP ribose (ADPR), an NAD-metabolite produced under oxidative stress and neurodegenerative conditions, suggests a role in neurological disorders. We provide a central concept between triple-site ligand binding and the channel gating of human TRPM2. We show consecutive structural rearrangements and channel activation of TRPM2 induced by binding of ADPR in two indispensable locations, and the binding of Ca in the transmembrane domain. The 8-Br-cADPR-an antagonist of cADPR-binds only to the MHR1/2 domain and inhibits TRPM2 by stabilizing the channel in an apo-like conformation. We conclude that MHR1/2 acts as a orthostatic ligand-binding site for TRPM2. The NUDT9-H domain binds to a second ADPR to assist channel activation in vertebrates, but not necessary in invertebrates. Our work provides insights into the gating mechanism of human TRPM2 and its pharmacology.
History
DepositionJul 18, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 25, 2019Provider: repository / Type: Initial release
Revision 1.1Dec 18, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.2Mar 20, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / entity / pdbx_entity_nonpoly
Item: _chem_comp.name / _database_2.pdbx_DOI ..._chem_comp.name / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _entity.pdbx_description / _pdbx_entity_nonpoly.name

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-20482
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Transient receptor potential cation channel subfamily M member 2
B: Transient receptor potential cation channel subfamily M member 2
C: Transient receptor potential cation channel subfamily M member 2
D: Transient receptor potential cation channel subfamily M member 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)691,76512
Polymers689,1204
Non-polymers2,6458
Water0
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area18840 Å2
ΔGint-226 kcal/mol
Surface area249500 Å2

-
Components

#1: Protein
Transient receptor potential cation channel subfamily M member 2 / TRPM2 / Estrogen-responsive element-associated gene 1 protein / Long transient receptor potential ...TRPM2 / Estrogen-responsive element-associated gene 1 protein / Long transient receptor potential channel 2 / LTrpC2 / Transient receptor potential channel 7 / TrpC7 / Transient receptor potential melastatin 2


Mass: 172280.062 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TRPM2, EREG1, KNP3, LTRPC2, TRPC7 / Production host: Homo sapiens (human) / References: UniProt: O94759
#2: Chemical
ChemComp-CV1 / (2R,3R,4S,5R,13R,14S,15R,16R)-24-amino-18-bromo-3,4,14,15-tetrahydroxy-7,9,11,25,26-pentaoxa-17,19,22-triaza-1-azonia-8 ,10-diphosphapentacyclo[18.3.1.1^2,5^.1^13,16^.0^17,21^]hexacosa-1(24),18,20,22-tetraene-8,10-diolate 8,10-dioxide / 8-BROMO-CYCLIC-ADP-RIBOSE


Mass: 621.204 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C15H21BrN5O13P2 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Ca / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: human TRPM2 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportDetails: unspecified
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm
Specimen holderCryogen: NITROGEN
Image recordingAverage exposure time: 8 sec. / Electron dose: 6.8 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k)
Image scansMovie frames/image: 40 / Used frames/image: 1-40

-
Processing

EM software
IDNameVersionCategory
2SerialEMimage acquisition
4GctfCTF correction
9PHENIXmodel refinement
10RELION3initial Euler assignment
11RELION3final Euler assignment
12RELION3classification
13RELION33D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 102259 / Symmetry type: POINT
Atomic model buildingProtocol: AB INITIO MODEL / Space: REAL

+
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