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Open data
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Basic information
Entry | Database: PDB / ID: 7vq2 | |||||||||
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Title | Structure of Apo-hsTRPM2 channel TM domain | |||||||||
![]() | Transient receptor potential cation channel subfamily M member 2 | |||||||||
![]() | TRANSPORT PROTEIN / channel / trpm2 / Selectivity Filter / TM domain | |||||||||
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 / 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 / response to purine-containing compound / ligand-gated calcium channel activity / 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 / : / ficolin-1-rich granule membrane / calcium ion import across plasma 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 / 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 | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.68 Å | |||||||||
![]() | Yu, X.F. / Xie, Y. / Zhang, X.K. / Ma, C. / Guo, J.T. / Yang, F. / Yang, W. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural and functional basis of the selectivity filter as a gate in human TRPM2 channel. Authors: Xiafei Yu / Yuan Xie / Xiaokang Zhang / Cheng Ma / Likun Liu / Wenxuan Zhen / Lingyi Xu / Jianmin Zhang / Yan Liang / Lixia Zhao / Xiuxia Gao / Peilin Yu / Jianhong Luo / Lin-Hua Jiang / Yan ...Authors: Xiafei Yu / Yuan Xie / Xiaokang Zhang / Cheng Ma / Likun Liu / Wenxuan Zhen / Lingyi Xu / Jianmin Zhang / Yan Liang / Lixia Zhao / Xiuxia Gao / Peilin Yu / Jianhong Luo / Lin-Hua Jiang / Yan Nie / Fan Yang / Jiangtao Guo / Wei Yang / ![]() Abstract: Transient receptor potential melastatin 2 (TRPM2), a Ca-permeable cation channel, is gated by intracellular adenosine diphosphate ribose (ADPR), Ca, warm temperature, and oxidative stress. It is ...Transient receptor potential melastatin 2 (TRPM2), a Ca-permeable cation channel, is gated by intracellular adenosine diphosphate ribose (ADPR), Ca, warm temperature, and oxidative stress. It is critically involved in physiological and pathological processes ranging from inflammation to stroke to neurodegeneration. At present, the channel's gating and ion permeation mechanisms, such as the location and identity of the selectivity filter, remain ambiguous. Here, we report the cryo-electron microscopy (cryo-EM) structure of human TRPM2 in nanodisc in the ligand-free state. Cryo-EM map-guided computational modeling and patch-clamp recording further identify a quadruple-residue motif as the ion selectivity filter, which adopts a restrictive conformation in the closed state and acts as a gate, profoundly contrasting with its widely open conformation in the Nematostella vectensis TRPM2. Our study reveals the gating of human TRPM2 by the filter and demonstrates the feasibility of using cryo-EM in conjunction with computational modeling and functional studies to garner structural information for intrinsically dynamic but functionally important domains. | |||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 466.5 KB | Display | ![]() |
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PDB format | ![]() | 394.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 807.1 KB | Display | ![]() |
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Full document | ![]() | 818.5 KB | Display | |
Data in XML | ![]() | 42.2 KB | Display | |
Data in CIF | ![]() | 58.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 32083MC ![]() 7vq1C 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: 40967.398 Da / Num. of mol.: 4 / Fragment: TM domain 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: TRPM2 / Type: CELL / 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 |
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 | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.68 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 68530 / Symmetry type: POINT |