[English] 日本語
Yorodumi- PDB-6drj: Structure of TRPM2 ion channel receptor by single particle electr... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6drj | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of TRPM2 ion channel receptor by single particle electron cryo-microscopy, ADPR/Ca2+ bound state | ||||||
Components | Transient receptor potential cation channel, subfamily M, member 2 | ||||||
Keywords | TRANSPORT PROTEIN | ||||||
Function / homology | Function and homology information TRP channels / Neutrophil degranulation / ADP-D-ribose binding / mono-ADP-D-ribose binding / ligand-gated calcium channel activity / ligand-gated monoatomic cation channel activity / release of sequestered calcium ion into cytosol / calcium ion transmembrane transport / calcium channel activity / monoatomic ion channel activity ...TRP channels / Neutrophil degranulation / ADP-D-ribose binding / mono-ADP-D-ribose binding / ligand-gated calcium channel activity / ligand-gated monoatomic cation channel activity / release of sequestered calcium ion into cytosol / calcium ion transmembrane transport / calcium channel activity / monoatomic ion channel activity / protein homotetramerization / calcium ion binding / plasma membrane Similarity search - Function | ||||||
Biological species | Danio rerio (zebrafish) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
Authors | Du, J. / Lu, W. / Huang, Y. / Winkler, P. / Sun, W. | ||||||
Citation | Journal: Nature / Year: 2018 Title: Architecture of the TRPM2 channel and its activation mechanism by ADP-ribose and calcium. Authors: Yihe Huang / Paige A Winkler / Weinan Sun / Wei Lü / Juan Du / Abstract: Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable, non-selective cation channel that has an essential role in diverse physiological processes such as core body temperature ...Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable, non-selective cation channel that has an essential role in diverse physiological processes such as core body temperature regulation, immune response and apoptosis. TRPM2 is polymodal and can be activated by a wide range of stimuli, including temperature, oxidative stress and NAD-related metabolites such as ADP-ribose (ADPR). Its activation results in both Ca entry across the plasma membrane and Ca release from lysosomes, and has been linked to diseases such as ischaemia-reperfusion injury, bipolar disorder and Alzheimer's disease. Here we report the cryo-electron microscopy structures of the zebrafish TRPM2 in the apo resting (closed) state and in the ADPR/Ca-bound active (open) state, in which the characteristic NUDT9-H domains hang underneath the MHR1/2 domain. We identify an ADPR-binding site located in the bi-lobed structure of the MHR1/2 domain. Our results provide an insight into the mechanism of activation of the TRPM channel family and define a framework for the development of therapeutic agents to treat neurodegenerative diseases and temperature-related pathological conditions. | ||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6drj.cif.gz | 832.8 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6drj.ent.gz | 663.7 KB | Display | PDB format |
PDBx/mmJSON format | 6drj.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6drj_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 6drj_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 6drj_validation.xml.gz | 120.2 KB | Display | |
Data in CIF | 6drj_validation.cif.gz | 186.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dr/6drj ftp://data.pdbj.org/pub/pdb/validation_reports/dr/6drj | HTTPS FTP |
-Related structure data
Related structure data | 7999MC 8901C 6drkC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 168383.469 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Danio rerio (zebrafish) / Gene: trpm2 / Cell line (production host): HEK293 GnTI- / Production host: Homo sapiens (human) / References: UniProt: A0A0R4IN04, UniProt: A0A0R4IMY7*PLUS #2: Chemical | ChemComp-APR / #3: Chemical | ChemComp-CA / |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Ion channel 1 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
---|---|
Molecular weight | Value: 0.5 MDa / Experimental value: YES |
Source (natural) | Organism: Danio rerio (zebrafish) |
Source (recombinant) | Organism: Mammalia (mammals) |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 45 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: dev_3084: / Classification: refinement |
---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 227007 / Symmetry type: POINT |