+Open data
-Basic information
Entry | Database: PDB / ID: 6mix | ||||||
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Title | Human TRPM2 ion channel in apo state | ||||||
Components | Transient receptor potential cation channel subfamily M member 2 | ||||||
Keywords | MEMBRANE PROTEIN / Channel / TRPM2 / TRP / ADPR / ADP-ribose / NUDT9H / NUDT9 / calcium / ion channel | ||||||
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 / regulation of filopodium assembly / cellular response to temperature stimulus / 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 / regulation of filopodium assembly / cellular response to temperature stimulus / sodium channel activity / TRP channels / response to hydroperoxide / calcium ion transmembrane import into cytosol / dendritic cell chemotaxis / temperature homeostasis / intracellularly gated calcium channel activity / tertiary granule membrane / calcium ion import across plasma membrane / ficolin-1-rich granule membrane / : / specific granule membrane / monoatomic cation channel activity / release of sequestered calcium ion into cytosol / cellular response to calcium ion / cell projection / regulation of actin cytoskeleton organization / calcium ion transmembrane transport / 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 | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å | ||||||
Authors | Wang, L. / Fu, T.M. / Xia, S. / Wu, H. | ||||||
Citation | Journal: Science / Year: 2018 Title: Structures and gating mechanism of human TRPM2. Authors: Longfei Wang / Tian-Min Fu / Yiming Zhou / Shiyu Xia / Anna Greka / Hao Wu / Abstract: Transient receptor potential (TRP) melastatin 2 (TRPM2) is a cation channel associated with numerous diseases. It has a C-terminal NUDT9 homology (NUDT9H) domain responsible for binding adenosine ...Transient receptor potential (TRP) melastatin 2 (TRPM2) is a cation channel associated with numerous diseases. It has a C-terminal NUDT9 homology (NUDT9H) domain responsible for binding adenosine diphosphate (ADP)-ribose (ADPR), and both ADPR and calcium (Ca) are required for TRPM2 activation. Here we report cryo-electron microscopy structures of human TRPM2 alone, with ADPR, and with ADPR and Ca NUDT9H forms both intra- and intersubunit interactions with the N-terminal TRPM homology region (MHR1/2/3) in the apo state but undergoes conformational changes upon ADPR binding, resulting in rotation of MHR1/2 and disruption of the intersubunit interaction. The binding of Ca further engages transmembrane helices and the conserved TRP helix to cause conformational changes at the MHR arm and the lower gating pore to potentiate channel opening. These findings explain the molecular mechanism of concerted TRPM2 gating by ADPR and Ca and provide insights into the gating mechanism of other TRP channels. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6mix.cif.gz | 930.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6mix.ent.gz | 782.3 KB | Display | PDB format |
PDBx/mmJSON format | 6mix.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mi/6mix ftp://data.pdbj.org/pub/pdb/validation_reports/mi/6mix | HTTPS FTP |
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-Related structure data
Related structure data | 9132MUC 9133C 9134C 6mizC 6mj2C M: map data used to model this data U: unfit; in different coordinate system*YM C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 171416.188 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 |
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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 |
-Sample preparation
Component | Name: Human TRPM2 ion channel / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 70.12 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.14_3260: / Classification: refinement |
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CTF correction | Type: NONE |
3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 34477 / Symmetry type: POINT |