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- PDB-8srb: Cryo-EM structure of TRPM2 chanzyme in the presence of EDTA and A... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8srb | |||||||||||||||
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Title | Cryo-EM structure of TRPM2 chanzyme in the presence of EDTA and ADP-ribose | |||||||||||||||
![]() | TRPM2 chanzyme | |||||||||||||||
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Function / homology | ![]() | |||||||||||||||
Biological species | ![]() ![]() | |||||||||||||||
Method | ![]() ![]() ![]() | |||||||||||||||
![]() | Huang, Y. / Kumar, S. / Lu, W. / Du, J. | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Coupling enzymatic activity and gating in an ancient TRPM chanzyme and its molecular evolution. Authors: Yihe Huang / Sushant Kumar / Junuk Lee / Wei Lü / Juan Du / ![]() Abstract: Channel enzymes represent a class of ion channels with enzymatic activity directly or indirectly linked to their channel function. We investigated a TRPM2 chanzyme from choanoflagellates that ...Channel enzymes represent a class of ion channels with enzymatic activity directly or indirectly linked to their channel function. We investigated a TRPM2 chanzyme from choanoflagellates that integrates two seemingly incompatible functions into a single peptide: a channel module activated by ADP-ribose with high open probability and an enzyme module (NUDT9-H domain) consuming ADP-ribose at a remarkably slow rate. Using time-resolved cryogenic-electron microscopy, we captured a complete series of structural snapshots of gating and catalytic cycles, revealing the coupling mechanism between channel gating and enzymatic activity. The slow kinetics of the NUDT9-H enzyme module confers a self-regulatory mechanism: ADPR binding triggers NUDT9-H tetramerization, promoting channel opening, while subsequent hydrolysis reduces local ADPR, inducing channel closure. We further demonstrated how the NUDT9-H domain has evolved from a structurally semi-independent ADP-ribose hydrolase module in early species to a fully integrated component of a gating ring essential for channel activation in advanced species. | |||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 1003.9 KB | Display | ![]() |
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PDB format | ![]() | 794.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 40725MC ![]() 8sr7C ![]() 8sr8C ![]() 8sr9C ![]() 8sraC ![]() 8srcC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
#1: Protein | Mass: 168252.484 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #2: Chemical | ChemComp-APR / #3: Chemical | ChemComp-CLR / ![]() Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: TRPM2 chanzyme in the presence of EDTA and ADP-ribose / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 8 |
Specimen | Conc.: 8.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
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![]() |
Image recording | Average exposure time: 0.02 sec. / Electron dose: 49 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
CTF correction![]() | Type: NONE | ||||||||||||||||||||||||
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Symmetry | Point symmetry![]() ![]() | ||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 2.82 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 11628 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL | ||||||||||||||||||||||||
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