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- PDB-7x6i: Cryo-EM structure of the human TRPC5 ion channel in complex with ... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7x6i | ||||||
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Title | Cryo-EM structure of the human TRPC5 ion channel in complex with G alpha i3 subunits, class1 | ||||||
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![]() | METAL TRANSPORT / transient receptor potential | ||||||
Function / homology | ![]() regulation of membrane hyperpolarization / phosphatidylserine exposure on apoptotic cell surface / negative regulation of dendrite morphogenesis / Role of second messengers in netrin-1 signaling / store-operated calcium channel activity / cation channel complex / negative regulation of adenylate cyclase activity / inositol 1,4,5 trisphosphate binding / actinin binding / GTP metabolic process ...regulation of membrane hyperpolarization / phosphatidylserine exposure on apoptotic cell surface / negative regulation of dendrite morphogenesis / Role of second messengers in netrin-1 signaling / store-operated calcium channel activity / cation channel complex / negative regulation of adenylate cyclase activity / inositol 1,4,5 trisphosphate binding / actinin binding / GTP metabolic process / TRP channels / G protein-coupled dopamine receptor signaling pathway / clathrin binding / positive regulation of macroautophagy / Adenylate cyclase inhibitory pathway / positive regulation of axon extension / calcium channel complex / regulation of cytosolic calcium ion concentration / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / positive regulation of neuron differentiation / positive regulation of peptidyl-threonine phosphorylation / G protein-coupled receptor binding / calcium ion transmembrane transport / G-protein beta/gamma-subunit complex binding / calcium channel activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / neuron differentiation / ADP signalling through P2Y purinoceptor 12 / G alpha (z) signalling events / ADORA2B mediated anti-inflammatory cytokines production / GPER1 signaling / GDP binding / calcium ion transport / heterotrimeric G-protein complex / nervous system development / actin binding / midbody / G alpha (i) signalling events / growth cone / positive regulation of cytosolic calcium ion concentration / ATPase binding / G alpha (s) signalling events / neuron apoptotic process / Extra-nuclear estrogen signaling / cell cycle / lysosomal membrane / cell division / GTPase activity / centrosome / neuronal cell body / dendrite / positive regulation of cell population proliferation / nucleolus / GTP binding / Golgi apparatus / extracellular exosome / nucleoplasm / membrane / metal ion binding / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.93 Å | ||||||
![]() | Won, J. / Jeong, H. / Lee, H.H. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular architecture of the Gα-bound TRPC5 ion channel. Authors: Jongdae Won / Jinsung Kim / Hyeongseop Jeong / Jinhyeong Kim / Shasha Feng / Byeongseok Jeong / Misun Kwak / Juyeon Ko / Wonpil Im / Insuk So / Hyung Ho Lee / ![]() ![]() Abstract: G-protein coupled receptors (GPCRs) and ion channels serve as key molecular switches through which extracellular stimuli are transformed into intracellular effects, and it has long been postulated ...G-protein coupled receptors (GPCRs) and ion channels serve as key molecular switches through which extracellular stimuli are transformed into intracellular effects, and it has long been postulated that ion channels are direct effector molecules of the alpha subunit of G-proteins (Gα). However, no complete structural evidence supporting the direct interaction between Gα and ion channels is available. Here, we present the cryo-electron microscopy structures of the human transient receptor potential canonical 5 (TRPC5)-Gα complexes with a 4:4 stoichiometry in lipid nanodiscs. Remarkably, Gα binds to the ankyrin repeat edge of TRPC5 ~ 50 Å away from the cell membrane. Electrophysiological analysis shows that Gα increases the sensitivity of TRPC5 to phosphatidylinositol 4,5-bisphosphate (PIP), thereby rendering TRPC5 more easily opened in the cell membrane, where the concentration of PIP is physiologically regulated. Our results demonstrate that ion channels are one of the direct effector molecules of Gα proteins triggered by GPCR activation-providing a structural framework for unraveling the crosstalk between two major classes of transmembrane proteins: GPCRs and ion channels. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 725.2 KB | Display | ![]() |
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PDB format | ![]() | 604.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 1.6 MB | Display | ![]() |
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Full document | ![]() | 1.6 MB | Display | |
Data in XML | ![]() | 104 KB | Display | |
Data in CIF | ![]() | 148.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 33022MC ![]() 7x6cC ![]() 8gvwC ![]() 8gvxC 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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Components
-Protein , 2 types, 8 molecules ABCDEFGH
#1: Protein | Mass: 89951.891 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Details: residues 766,767(SR) restriction enzyme, XbaI, residues 768-773(LEVLFQ) protease cleavage site, HRV-3C Source: (gene. exp.) ![]() ![]() #2: Protein | Mass: 41399.047 Da / Num. of mol.: 4 / Mutation: Q204L Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Non-polymers , 6 types, 24 molecules ![](data/chem/img/PTY.gif)
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#3: Chemical | ChemComp-PTY / #4: Chemical | ChemComp-Y01 / #5: Chemical | ChemComp-ZN / #6: Chemical | ChemComp-CA / #7: Chemical | ChemComp-YZY / ( #8: Chemical | ChemComp-GTP / |
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-Details
Has ligand of interest | Y |
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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
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||
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Source (recombinant) |
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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
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.93 Å / Resolution method: OTHER / Num. of particles: 18935 Details: We combined two different maps from the same dataset (D_1300028166_em-additional-volume_P1.map.V2 and D_1300028166_em-additional-volume_P2.map.V2) to generate a composite map (D_1300028166_ ...Details: We combined two different maps from the same dataset (D_1300028166_em-additional-volume_P1.map.V2 and D_1300028166_em-additional-volume_P2.map.V2) to generate a composite map (D_1300028166_em-volume_P1.map.V2). The density of the G protein area could not be visualized clearly in the consensus map of this EM dataset. Therefore, we performed focused classification and local refinement to improve the density of the G protein area using symmetry expanded particles with C4 symmetry imposition, which required more number of particles. Finally, the number of particles used to reconstruct additional volume data 2 (D_1300028166_em-additional-volume_P2.map.V2) is 18,935 and the number of particles used to reconstruct additional volume data 1 (D_1300028166_em-additional-volume_P1.map.V2) is 205,343. Furthermore, the resolution stated above is based on map resolution estimates calculated by a validation tool in Phenix, FSC (model) = 0.5. Symmetry type: POINT |