+
Open data
-
Basic information
Entry | Database: PDB / ID: 7vnr | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of human KCNQ4-ML213 complex in digitonin | ||||||
![]() |
| ||||||
![]() | ![]() ![]() ![]() ![]() | ||||||
Function / homology | ![]() Voltage gated Potassium channels / Sensory processing of sound by outer hair cells of the cochlea / Sensory processing of sound by inner hair cells of the cochlea / negative regulation of high voltage-gated calcium channel activity / inner ear morphogenesis / negative regulation of calcium ion export across plasma membrane / regulation of cardiac muscle cell action potential / positive regulation of ryanodine-sensitive calcium-release channel activity / regulation of cell communication by electrical coupling involved in cardiac conduction / negative regulation of peptidyl-threonine phosphorylation ...Voltage gated Potassium channels / Sensory processing of sound by outer hair cells of the cochlea / Sensory processing of sound by inner hair cells of the cochlea / negative regulation of high voltage-gated calcium channel activity / inner ear morphogenesis / negative regulation of calcium ion export across plasma membrane / regulation of cardiac muscle cell action potential / positive regulation of ryanodine-sensitive calcium-release channel activity / regulation of cell communication by electrical coupling involved in cardiac conduction / negative regulation of peptidyl-threonine phosphorylation / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Xu, F. / Zheng, Y. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() Title: Structural insights into the lipid and ligand regulation of a human neuronal KCNQ channel. Authors: You Zheng / Heng Liu / Yuxin Chen / Shaowei Dong / Fang Wang / Shengyi Wang / Geng-Lin Li / Yilai Shu / Fei Xu / ![]() Abstract: The KCNQ family (KCNQ1-KCNQ5) of voltage-gated potassium channels plays critical roles in many physiological and pathological processes. It is known that the channel opening of all KCNQs relies on ...The KCNQ family (KCNQ1-KCNQ5) of voltage-gated potassium channels plays critical roles in many physiological and pathological processes. It is known that the channel opening of all KCNQs relies on the signaling lipid molecule phosphatidylinositol 4,5-bisphosphate (PIP2). However, the molecular mechanism of PIP2 in modulating the opening of the four neuronal KCNQ channels (KCNQ2-KCNQ5), which are essential for regulating neuronal excitability, remains largely elusive. Here, we report the cryoelectron microscopy (cryo-EM) structures of human KCNQ4 determined in complex with the activator ML213 in the absence or presence of PIP2. Two PIP2 molecules are identified in the open-state structure of KCNQ4, which act as a bridge to couple the voltage-sensing domain (VSD) and pore domain (PD) of KCNQ4 leading to the channel opening. Our findings reveal the binding sites and activation mechanisms of ML213 and PIP2 for neuronal KCNQ channels, providing a framework for therapeutic intervention targeting on these important channels. | ||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 403.3 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 310.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 32046MC ![]() 7vnpC ![]() 7vnqC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | Mass: 116541.383 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Details: The fusion protein of Potassium voltage-gated channel subfamily KQT member 4, linker, and Maltodextrin-binding protein Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() Gene: KCNQ4, ECBD_4002 / Strain: B / BL21-DE3 / Production host: ![]() ![]() #2: Protein | ![]() Mass: 16852.545 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #3: Chemical | ChemComp-7YV / ( #4: Chemical | Has ligand of interest | Y | |
---|
-Experimental details
-Experiment
Experiment | Method: ![]() |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
-
Sample preparation
Component | Name: KCNQ4-ML213 complex in digitonin / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 4.8 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
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: DARK FIELD |
Image recording | Electron dose: 16.8 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-
Processing
CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
---|---|
3D reconstruction![]() | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 126225 / Symmetry type: POINT |