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- PDB-7dxf: Structure of BTDM-bound human TRPC6 nanodisc at 2.9 angstrom in h... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7dxf | |||||||||||||||
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Title | Structure of BTDM-bound human TRPC6 nanodisc at 2.9 angstrom in high calcium state | |||||||||||||||
![]() | Short transient receptor potential channel 6 | |||||||||||||||
![]() | MEMBRANE PROTEIN / TRPC6 / TRPC / calcium / BTDM / FSGS / channel | |||||||||||||||
Function / homology | ![]() positive regulation of ion transmembrane transporter activity / slit diaphragm / Role of second messengers in netrin-1 signaling / store-operated calcium channel activity / Elevation of cytosolic Ca2+ levels / Effects of PIP2 hydrolysis / cation channel complex / inositol 1,4,5 trisphosphate binding / positive regulation of calcium ion transport / TRP channels ...positive regulation of ion transmembrane transporter activity / slit diaphragm / Role of second messengers in netrin-1 signaling / store-operated calcium channel activity / Elevation of cytosolic Ca2+ levels / Effects of PIP2 hydrolysis / cation channel complex / inositol 1,4,5 trisphosphate binding / positive regulation of calcium ion transport / TRP channels / monoatomic cation transport / single fertilization / monoatomic cation channel activity / regulation of cytosolic calcium ion concentration / calcium ion transmembrane transport / calcium channel activity / positive regulation of cytosolic calcium ion concentration / protein homodimerization activity / membrane / plasma membrane / cytoplasm Similarity search - Function | |||||||||||||||
Biological species | ![]() | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||||||||
![]() | Chen, L. / Guo, W. | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural mechanism of human TRPC3 and TRPC6 channel regulation by their intracellular calcium-binding sites. Authors: Wenjun Guo / Qinglin Tang / Miao Wei / Yunlu Kang / Jing-Xiang Wu / Lei Chen / ![]() Abstract: TRPC3 and TRPC6 channels are calcium-permeable non-selective cation channels that are involved in many physiological processes. The gain-of-function (GOF) mutations of TRPC6 lead to familial focal ...TRPC3 and TRPC6 channels are calcium-permeable non-selective cation channels that are involved in many physiological processes. The gain-of-function (GOF) mutations of TRPC6 lead to familial focal segmental glomerulosclerosis (FSGS) in humans, but their pathogenic mechanism remains elusive. Here, we report the cryo-EM structures of human TRPC3 in both high-calcium and low-calcium conditions. Based on these structures and accompanying electrophysiological studies, we identified both inhibitory and activating calcium-binding sites in TRPC3 that couple intracellular calcium concentrations to the basal channel activity. These calcium sensors are also structurally and functionally conserved in TRPC6. We uncovered that the GOF mutations of TRPC6 activate the channel by allosterically abolishing the inhibitory effects of intracellular calcium. Furthermore, structures of human TRPC6 in complex with two chemically distinct inhibitors bound at different ligand-binding pockets reveal different conformations of the transmembrane domain, providing templates for further structure-based drug design targeting TRPC6-related diseases such as FSGS. | |||||||||||||||
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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PDBx/mmCIF format | ![]() | 576.4 KB | Display | ![]() |
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PDB format | ![]() | 465.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 30907MC ![]() 7dxbC ![]() 7dxcC ![]() 7dxdC ![]() 7dxeC ![]() 7dxgC 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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1 |
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Components
-Protein , 1 types, 4 molecules ABCD
#1: Protein | Mass: 106453.242 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Non-polymers , 6 types, 40 molecules ![](data/chem/img/ZN.gif)
![](data/chem/img/W99.gif)
![](data/chem/img/Y01.gif)
![](data/chem/img/CA.gif)
![](data/chem/img/POV.gif)
![](data/chem/img/98R.gif)
![](data/chem/img/W99.gif)
![](data/chem/img/Y01.gif)
![](data/chem/img/CA.gif)
![](data/chem/img/POV.gif)
![](data/chem/img/98R.gif)
#2: Chemical | ChemComp-ZN / #3: Chemical | ChemComp-W99 / [ #4: Chemical | ChemComp-Y01 / #5: Chemical | ChemComp-CA / #6: Chemical | ChemComp-POV / ( #7: Chemical | ChemComp-98R / [( |
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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
Component | Name: human transient receptor potential channel 6 tetramer / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.5 |
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: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 95686 / Symmetry type: POINT |