[English] 日本語
Yorodumi
- EMDB-20480: Human TRPM2 bound to ADPR and calcium -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-20480
TitleHuman TRPM2 bound to ADPR and calcium
Map data
Samplehuman TRPM2
  • Transient receptor potential cation channel subfamily M member 2
  • (ligand) x 2
Function / homology
Function and homology information


cellular response to purine-containing compound / response to purine-containing compound / mono-ADP-D-ribose binding / zinc ion transmembrane transport / cellular response to temperature stimulus / ligand-gated calcium channel activity / cation transmembrane transport / dendritic cell differentiation / metal ion transport / regulation of filopodium assembly ...cellular response to purine-containing compound / response to purine-containing compound / mono-ADP-D-ribose binding / zinc ion transmembrane transport / cellular response to temperature stimulus / ligand-gated calcium channel activity / cation transmembrane transport / dendritic cell differentiation / metal ion transport / regulation of filopodium assembly / temperature homeostasis / sodium channel activity / calcium ion transmembrane import into cytosol / TRP channels / calcium ion import across plasma membrane / regulation of actin cytoskeleton reorganization / dendritic cell chemotaxis / calcium-release channel activity / ficolin-1-rich granule membrane / tertiary granule membrane / release of sequestered calcium ion into cytosol / calcium-mediated signaling using intracellular calcium source / cation channel activity / specific granule membrane / cellular response to calcium ion / calcium channel activity / calcium ion transmembrane transport / cell projection / calcium ion transport / cellular response to hydrogen peroxide / lysosomal membrane / cytoplasmic vesicle membrane / perikaryon / protein homotetramerization / lysosome / Neutrophil degranulation / neutrophil degranulation / calcium ion binding / integral component of plasma membrane / plasma membrane
Similarity search - Function
Transient receptor potential cation channel subfamily M member 2 / SLOG in TRPM / TRPM, SLOG domain / NUDIX hydrolase domain / Nudix hydrolase domain profile. / NUDIX hydrolase-like domain superfamily / Ion transport domain / Ion transport protein
Similarity search - Domain/homology
Transient receptor potential cation channel subfamily M member 2
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.7 Å
AuthorsDu J / Lu W / Huang Y
Funding support United States, 1 items
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, 2019-
Header (metadata) releaseJul 31, 2019-
Map releaseSep 25, 2019-
UpdateDec 18, 2019-
Current statusDec 18, 2019Processing site: RCSB / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.0085
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.0085
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-6pus
  • Surface level: 0.0085
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

-
Map

FileDownload / File: emd_20480.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.07 Å/pix.
x 300 pix.
= 322.2 Å
1.07 Å/pix.
x 300 pix.
= 322.2 Å
1.07 Å/pix.
x 300 pix.
= 322.2 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.074 Å
Density
Contour LevelBy AUTHOR: 0.0085 / Movie #1: 0.0085
Minimum - Maximum-0.012010243 - 0.03683162
Average (Standard dev.)0.00002725957 (±0.0021983143)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 322.2 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.0741.0741.074
M x/y/z300300300
origin x/y/z0.0000.0000.000
length x/y/z322.200322.200322.200
α/β/γ90.00090.00090.000
start NX/NY/NZ1548552
NX/NY/NZ198170217
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS300300300
D min/max/mean-0.0120.0370.000

-
Supplemental data

-
Sample components

-
Entire human TRPM2

EntireName: human TRPM2 / Number of components: 4

-
Component #1: protein, human TRPM2

ProteinName: human TRPM2 / Recombinant expression: No
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Homo sapiens (human)

-
Component #2: protein, Transient receptor potential cation channel subfamily M ...

ProteinName: Transient receptor potential cation channel subfamily M member 2
Number of Copies: 4 / Recombinant expression: No
MassTheoretical: 172.280062 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Homo sapiens (human)

-
Component #3: ligand, ADENOSINE-5-DIPHOSPHORIBOSE

LigandName: ADENOSINE-5-DIPHOSPHORIBOSE / Number of Copies: 8 / Recombinant expression: No
MassTheoretical: 0.559316 kDa

-
Component #4: ligand, CALCIUM ION

LigandName: CALCIUM IONCalcium / Number of Copies: 4 / Recombinant expression: No
MassTheoretical: 4.007805 MDa

-
Experimental details

-
Sample preparation

SpecimenSpecimen state: Particle / Method: cryo EM
Sample solutionpH: 8
Support filmunspecified
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
ImagingMicroscope: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Electron dose: 6.8 e/Å2 / Illumination mode: FLOOD BEAM
LensCs: 2.7 mm / Imaging mode: BRIGHT FIELD / Defocus: 1000.0 - 2500.0 nm
Specimen HolderModel: OTHER
CameraDetector: GATAN K2 SUMMIT (4k x 4k)

-
Image processing

ProcessingMethod: single particle reconstruction / Number of projections: 287184
3D reconstructionSoftware: RELION / Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF

-
Atomic model buiding

Modeling #1Refinement space: REAL
Output model

+
About Yorodumi

-
News

-
Aug 12, 2020. New: Covid-19 info

New: Covid-19 info

  • 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. New: 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. (see PDBe EMDB page)
  • 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 at PDBe / 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. See below links for details.
  • 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

+
Jun 16, 2017. Omokage search with filter

Omokage search with filter

  • Result of Omokage search can be filtered by keywords and the database types

Related info.:Omokage search

Read more

-
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.

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