[English] 日本語
![](img/lk-miru.gif)
- PDB-8si7: Cryo-EM structure of TRPM7 in GDN detergent in complex with inhib... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 8si7 | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of TRPM7 in GDN detergent in complex with inhibitor VER155008 in closed state | ||||||||||||||||||
![]() | Transient receptor potential cation channel subfamily M member 7 | ||||||||||||||||||
![]() | MEMBRANE PROTEIN / transient receptor potential M family member 7 / TRP / channel / TRPM7 / TRP channels / magnesium channel / inhibitor / ligand / VER155008 | ||||||||||||||||||
Function / homology | ![]() intracellular magnesium ion homeostasis / calcium-dependent cell-matrix adhesion / monoatomic cation homeostasis / varicosity / TRP channels / actomyosin structure organization / myosin binding / monoatomic cation transmembrane transport / necroptotic process / monoatomic cation channel activity ...intracellular magnesium ion homeostasis / calcium-dependent cell-matrix adhesion / monoatomic cation homeostasis / varicosity / TRP channels / actomyosin structure organization / myosin binding / monoatomic cation transmembrane transport / necroptotic process / monoatomic cation channel activity / ruffle / protein tetramerization / calcium channel activity / memory / synaptic vesicle membrane / calcium ion transport / kinase activity / actin binding / non-specific serine/threonine protein kinase / protein kinase activity / positive regulation of apoptotic process / protein serine kinase activity / protein serine/threonine kinase activity / neuronal cell body / ATP binding / metal ion binding / plasma membrane Similarity search - Function | ||||||||||||||||||
Biological species | ![]() ![]() | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.59 Å | ||||||||||||||||||
![]() | Nadezhdin, K.D. / Neuberger, A. / Sobolevsky, A.I. | ||||||||||||||||||
Funding support | ![]() ![]()
| ||||||||||||||||||
![]() | ![]() Title: Structural mechanisms of TRPM7 activation and inhibition. Authors: Kirill D Nadezhdin / Leonor Correia / Chamali Narangoda / Dhilon S Patel / Arthur Neuberger / Thomas Gudermann / Maria G Kurnikova / Vladimir Chubanov / Alexander I Sobolevsky / ![]() ![]() Abstract: The transient receptor potential channel TRPM7 is a master regulator of the organismal balance of divalent cations that plays an essential role in embryonic development, immune responses, cell ...The transient receptor potential channel TRPM7 is a master regulator of the organismal balance of divalent cations that plays an essential role in embryonic development, immune responses, cell mobility, proliferation, and differentiation. TRPM7 is implicated in neuronal and cardiovascular disorders, tumor progression and has emerged as a new drug target. Here we use cryo-EM, functional analysis, and molecular dynamics simulations to uncover two distinct structural mechanisms of TRPM7 activation by a gain-of-function mutation and by the agonist naltriben, which show different conformational dynamics and domain involvement. We identify a binding site for highly potent and selective inhibitors and show that they act by stabilizing the TRPM7 closed state. The discovered structural mechanisms provide foundations for understanding the molecular basis of TRPM7 channelopathies and drug development. | ||||||||||||||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 1.6 MB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 1.4 MB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 40501MC ![]() 8si2C ![]() 8si3C ![]() 8si4C ![]() 8si5C ![]() 8si6C ![]() 8si8C ![]() 8siaC ![]() 8sibC C: citing same article ( M: map data used to model this data |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
-Protein , 1 types, 4 molecules ABCD
#1: Protein | Mass: 146888.875 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: Q923J1, non-specific serine/threonine protein kinase |
---|
-Non-polymers , 6 types, 221 molecules ![](data/chem/img/POV.gif)
![](data/chem/img/3FD.gif)
![](data/chem/img/CLR.gif)
![](data/chem/img/DU0.gif)
![](data/chem/img/CA.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/3FD.gif)
![](data/chem/img/CLR.gif)
![](data/chem/img/DU0.gif)
![](data/chem/img/CA.gif)
![](data/chem/img/HOH.gif)
#2: Chemical | ChemComp-POV / ( #3: Chemical | ChemComp-3FD / #4: Chemical | ChemComp-CLR / #5: Chemical | ChemComp-DU0 / #6: Chemical | ChemComp-CA / | #7: Water | ChemComp-HOH / | |
---|
-Details
Has ligand of interest | Y |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: sample 1 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | ||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Value: 0.7 MDa / 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: NO / Vitrification applied: YES / Details: mouse TRPM7 | ||||||||||||||||||||||||||||||
Specimen support | Grid type: C-flat-1.2/1.3 | ||||||||||||||||||||||||||||||
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 / Nominal defocus max: 1500 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm |
Image recording | Average exposure time: 2.5 sec. / Electron dose: 58 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 5989 |
Image scans | Width: 5760 / Height: 4092 |
-
Processing
EM software |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: NONE | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1425193 | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.59 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 197764 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Space: REAL | ||||||||||||||||||||||||
Refine LS restraints |
|