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Open data
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Basic information
Entry | Database: PDB / ID: 6puo | ||||||
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Title | Human TRPM2 in the apo state | ||||||
![]() | Transient receptor potential cation channel subfamily M member 2 | ||||||
![]() | TRANSPORT PROTEIN / TRPM2 channel / apo state | ||||||
Function / homology | ![]() cellular response to purine-containing compound / mono-ADP-D-ribose binding / manganese ion transmembrane transporter activity / zinc ion transmembrane transport / dendritic cell differentiation / response to purine-containing compound / ligand-gated calcium channel activity / regulation of filopodium assembly / cellular response to temperature stimulus / response to hydroperoxide ...cellular response to purine-containing compound / mono-ADP-D-ribose binding / manganese ion transmembrane transporter activity / zinc ion transmembrane transport / dendritic cell differentiation / response to purine-containing compound / ligand-gated calcium channel activity / regulation of filopodium assembly / cellular response to temperature stimulus / response to hydroperoxide / TRP channels / dendritic cell chemotaxis / sodium channel activity / calcium ion transmembrane import into cytosol / temperature homeostasis / calcium ion import across plasma membrane / intracellularly gated calcium channel activity / tertiary granule membrane / ficolin-1-rich granule membrane / monoatomic cation channel activity / specific granule membrane / release of sequestered calcium ion into cytosol / cellular response to calcium ion / cell projection / regulation of actin cytoskeleton organization / calcium ion transmembrane transport / cytoplasmic vesicle membrane / calcium channel activity / 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 | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
![]() | Du, J. / Lu, W. / Huang, Y. | ||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 877.8 KB | Display | ![]() |
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PDB format | ![]() | 686.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 20478MC ![]() 6purC ![]() 6pusC ![]() 6puuC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 172280.062 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: human TRPM2 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Average 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 scans | Movie frames/image: 40 / Used frames/image: 1-40 |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 161360 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL |