[English] 日本語
![](img/lk-miru.gif)
- PDB-7s88: Open apo-state cryo-EM structure of human TRPV6 in glyco-diosgeni... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 7s88 | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Open apo-state cryo-EM structure of human TRPV6 in glyco-diosgenin detergent | ||||||||||||||||||
![]() | Transient receptor potential cation channel subfamily V member 6 | ||||||||||||||||||
![]() | ![]() ![]() ![]() | ||||||||||||||||||
Function / homology | ![]() parathyroid hormone secretion / regulation of calcium ion-dependent exocytosis / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||||||||||||||
Biological species | ![]() ![]() | ||||||||||||||||||
Method | ![]() ![]() ![]() | ||||||||||||||||||
![]() | Neuberger, A. / Nadezhdin, K.D. / Sobolevsky, A.I. | ||||||||||||||||||
Funding support | ![]()
| ||||||||||||||||||
![]() | ![]() Title: Structural mechanisms of TRPV6 inhibition by ruthenium red and econazole. Authors: Arthur Neuberger / Kirill D Nadezhdin / Alexander I Sobolevsky / ![]() Abstract: TRPV6 is a calcium-selective ion channel implicated in epithelial Ca uptake. TRPV6 inhibitors are needed for the treatment of a broad range of diseases associated with disturbed calcium homeostasis, ...TRPV6 is a calcium-selective ion channel implicated in epithelial Ca uptake. TRPV6 inhibitors are needed for the treatment of a broad range of diseases associated with disturbed calcium homeostasis, including cancers. Here we combine cryo-EM, calcium imaging, and mutagenesis to explore molecular bases of human TRPV6 inhibition by the antifungal drug econazole and the universal ion channel blocker ruthenium red (RR). Econazole binds to an allosteric site at the channel's periphery, where it replaces a lipid. In contrast, RR inhibits TRPV6 by binding in the middle of the ion channel's selectivity filter and plugging its pore like a bottle cork. Despite different binding site locations, both inhibitors induce similar conformational changes in the channel resulting in closure of the gate formed by S6 helices bundle crossing. The uncovered molecular mechanisms of TRPV6 inhibition can guide the design of a new generation of clinically useful inhibitors. | ||||||||||||||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 487.6 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 408.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 24890MC ![]() 7s89C ![]() 7s8bC ![]() 7s8cC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
-Protein , 1 types, 4 molecules ABCD
#1: Protein | Mass: 78421.328 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
---|
-Non-polymers , 5 types, 209 molecules ![](data/chem/img/Y01.gif)
![](data/chem/img/PCW.gif)
![](data/chem/img/POV.gif)
![](data/chem/img/CA.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/PCW.gif)
![](data/chem/img/POV.gif)
![](data/chem/img/CA.gif)
![](data/chem/img/HOH.gif)
#2: Chemical | ChemComp-Y01 / #3: Chemical | ChemComp-PCW / #4: Chemical | ChemComp-POV / ( ![]() #5: Chemical | ChemComp-CA / | #6: Water | ChemComp-HOH / | ![]() |
---|
-Details
Has ligand of interest | N |
---|
-Experimental details
-Experiment
Experiment | Method: ![]() |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
-
Sample preparation
Component | Name: sample 1 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | ||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Units: MEGADALTONS / Experimental value: NO | ||||||||||||||||||||||||||||||
Source (natural) | Organism: ![]() ![]() | ||||||||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | ||||||||||||||||||||||||||||||
Buffer solution | pH: 8 | ||||||||||||||||||||||||||||||
Buffer component |
| ||||||||||||||||||||||||||||||
Specimen | Conc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() | ||||||||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil R1.2/1.3 | ||||||||||||||||||||||||||||||
Vitrification![]() | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: TFS KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() ![]() |
Image recording | Average exposure time: 3 sec. / Electron dose: 58 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 7904 |
Image scans | Width: 5760 / Height: 4092 |
-
Processing
EM software |
| ||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction![]() | Type: NONE | ||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 3117068 | ||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 2.69 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 276688 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 7K4A Accession code: 7K4A / Source name: PDB / Type: experimental model |