+Open data
-Basic information
Entry | Database: PDB / ID: 7phi | ||||||
---|---|---|---|---|---|---|---|
Title | Human voltage-gated potassium channel Kv3.1 (with Zn) | ||||||
Components | Potassium voltage-gated channel, Shaw-related subfamily, member 1Voltage-gated potassium channel | ||||||
Keywords | TRANSPORT PROTEIN / Channel / potassium channel / tetramer / voltage-gated / membrane protein | ||||||
Function / homology | Function and homology information globus pallidus development / response to nerve growth factor / response to light intensity / response to potassium ion / response to auditory stimulus / response to fibroblast growth factor / delayed rectifier potassium channel activity / corpus callosum development / positive regulation of potassium ion transmembrane transport / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential ...globus pallidus development / response to nerve growth factor / response to light intensity / response to potassium ion / response to auditory stimulus / response to fibroblast growth factor / delayed rectifier potassium channel activity / corpus callosum development / positive regulation of potassium ion transmembrane transport / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / Voltage gated Potassium channels / optic nerve development / neuronal cell body membrane / response to amine / voltage-gated potassium channel activity / kinesin binding / calyx of Held / axolemma / voltage-gated potassium channel complex / axon terminus / potassium ion transmembrane transport / dendrite membrane / cerebellum development / protein tetramerization / protein homooligomerization / potassium ion transport / response to toxic substance / cellular response to xenobiotic stimulus / presynaptic membrane / postsynaptic membrane / transmembrane transporter binding / cell surface / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | ||||||
Authors | Chi, G. / Qian, P. / Castro-Hartmann, P. / Venkaya, S. / Singh, N.K. / McKinley, G. / Mukhopadhyay, S.M.M. / Fernandez-Cid, A. / Marsden, B. / MacLean, E.M. ...Chi, G. / Qian, P. / Castro-Hartmann, P. / Venkaya, S. / Singh, N.K. / McKinley, G. / Mukhopadhyay, S.M.M. / Fernandez-Cid, A. / Marsden, B. / MacLean, E.M. / Pike, A.C.W. / Sader, K. / Burgess-Brown, N.A. / Duerr, K.L. | ||||||
Funding support | United Kingdom, 1items
| ||||||
Citation | Journal: Nat Commun / Year: 2022 Title: Cryo-EM structure of the human Kv3.1 channel reveals gating control by the cytoplasmic T1 domain. Authors: Gamma Chi / Qiansheng Liang / Akshay Sridhar / John B Cowgill / Kasim Sader / Mazdak Radjainia / Pu Qian / Pablo Castro-Hartmann / Shayla Venkaya / Nanki Kaur Singh / Gavin McKinley / ...Authors: Gamma Chi / Qiansheng Liang / Akshay Sridhar / John B Cowgill / Kasim Sader / Mazdak Radjainia / Pu Qian / Pablo Castro-Hartmann / Shayla Venkaya / Nanki Kaur Singh / Gavin McKinley / Alejandra Fernandez-Cid / Shubhashish M M Mukhopadhyay / Nicola A Burgess-Brown / Lucie Delemotte / Manuel Covarrubias / Katharina L Dürr / Abstract: Kv3 channels have distinctive gating kinetics tailored for rapid repolarization in fast-spiking neurons. Malfunction of this process due to genetic variants in the KCNC1 gene causes severe epileptic ...Kv3 channels have distinctive gating kinetics tailored for rapid repolarization in fast-spiking neurons. Malfunction of this process due to genetic variants in the KCNC1 gene causes severe epileptic disorders, yet the structural determinants for the unusual gating properties remain elusive. Here, we present cryo-electron microscopy structures of the human Kv3.1a channel, revealing a unique arrangement of the cytoplasmic tetramerization domain T1 which facilitates interactions with C-terminal axonal targeting motif and key components of the gating machinery. Additional interactions between S1/S2 linker and turret domain strengthen the interface between voltage sensor and pore domain. Supported by molecular dynamics simulations, electrophysiological and mutational analyses, we identify several residues in the S4/S5 linker which influence the gating kinetics and an electrostatic interaction between acidic residues in α6 of T1 and R449 in the pore-flanking S6T helices. These findings provide insights into gating control and disease mechanisms and may guide strategies for the design of pharmaceutical drugs targeting Kv3 channels. | ||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7phi.cif.gz | 287.7 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7phi.ent.gz | 234.9 KB | Display | PDB format |
PDBx/mmJSON format | 7phi.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ph/7phi ftp://data.pdbj.org/pub/pdb/validation_reports/ph/7phi | HTTPS FTP |
---|
-Related structure data
Related structure data | 13417MC 7phhC 7phkC 7phlC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 58850.078 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KCNC1 / Production host: Homo sapiens (human) / References: UniProt: Q3KNS8 #2: Chemical | ChemComp-PCF / #3: Chemical | ChemComp-ZN / #4: Chemical | ChemComp-K / Has ligand of interest | N | |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Homotetrameric complex of human Kv3.1 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
---|---|
Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 47.59 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM software | Name: EPU / Category: image acquisition | ||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C4 (4 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 133488 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|