[English] 日本語
![](img/lk-miru.gif)
- PDB-7ua1: Structure of PKA phosphorylated human RyR2-R2474S in the closed s... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 7ua1 | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of PKA phosphorylated human RyR2-R2474S in the closed state in the presence of ARM210 | ||||||
![]() |
| ||||||
![]() | ![]() ![]() | ||||||
Function / homology | ![]() junctional sarcoplasmic reticulum membrane / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Miotto, M.C. / Marks, A.R. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() Title: Structural analyses of human ryanodine receptor type 2 channels reveal the mechanisms for sudden cardiac death and treatment. Authors: Marco C Miotto / Gunnar Weninger / Haikel Dridi / Qi Yuan / Yang Liu / Anetta Wronska / Zephan Melville / Leah Sittenfeld / Steven Reiken / Andrew R Marks / ![]() Abstract: Ryanodine receptor type 2 (RyR2) mutations have been linked to an inherited form of exercise-induced sudden cardiac death called catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT ...Ryanodine receptor type 2 (RyR2) mutations have been linked to an inherited form of exercise-induced sudden cardiac death called catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT results from stress-induced sarcoplasmic reticular Ca leak via the mutant RyR2 channels during diastole. We present atomic models of human wild-type (WT) RyR2 and the CPVT mutant RyR2-R2474S determined by cryo-electron microscopy with overall resolutions in the range of 2.6 to 3.6 Å, and reaching local resolutions of 2.25 Å, unprecedented for RyR2 channels. Under nonactivating conditions, the RyR2-R2474S channel is in a "primed" state between the closed and open states of WT RyR2, rendering it more sensitive to activation that results in stress-induced Ca leak. The Rycal drug ARM210 binds to RyR2-R2474S, reverting the primed state toward the closed state. Together, these studies provide a mechanism for CPVT and for the therapeutic actions of ARM210. | ||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 2.9 MB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 26412MC ![]() 7u9qC ![]() 7u9rC ![]() 7u9tC ![]() 7u9xC ![]() 7u9zC ![]() 7ua3C ![]() 7ua4C ![]() 7ua5C ![]() 7ua9C M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | ![]() Mass: 565216.000 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #2: Protein | Mass: 11798.501 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() #3: Chemical | ChemComp-ZN / #4: Chemical | ChemComp-ATP / ![]() #5: Chemical | ChemComp-KVR / Has ligand of interest | Y | |
---|
-Experimental details
-Experiment
Experiment | Method: ![]() |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
-
Sample preparation
Component |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Source (natural) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Source (recombinant) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Buffer solution | pH: 7.4 Details: Xanthine was made fresh to avoid aggregation. Xanthine stock solution was 10 mM in NaOH 0.5 N. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Buffer component |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Specimen | Conc.: 2.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Vitrification![]() | Cryogen name: ETHANE |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() |
Image recording | Electron dose: 58 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-
Processing
EM software | Name: cryoSPARC / Category: CTF correction |
---|---|
CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3D reconstruction![]() | Resolution: 2.99 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 113172 / Symmetry type: POINT |
Atomic model building | PDB-ID: 7U9X |