+Open data
-Basic information
Entry | Database: PDB / ID: 7phl | ||||||
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Title | Human voltage-gated potassium channel Kv3.1 (with EDTA) | ||||||
Components | Potassium voltage-gated channel, Shaw-related subfamily, member 1 | ||||||
Keywords | TRANSPORT PROTEIN / Channel / potassium channel / tetramer / voltage-gated / membrane protein | ||||||
Function / homology | Function and homology information response to nerve growth factor / globus pallidus development / response to potassium ion / response to fibroblast growth factor / response to auditory stimulus / corpus callosum development / positive regulation of potassium ion transmembrane transport / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / response to light intensity / Voltage gated Potassium channels ...response to nerve growth factor / globus pallidus development / response to potassium ion / response to fibroblast growth factor / response to auditory stimulus / corpus callosum development / positive regulation of potassium ion transmembrane transport / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / response to light intensity / Voltage gated Potassium channels / delayed rectifier potassium channel activity / optic nerve development / neuronal cell body membrane / response to amine / voltage-gated potassium channel activity / action potential / kinesin binding / calyx of Held / axolemma / axon terminus / voltage-gated potassium channel complex / potassium ion transmembrane transport / dendrite membrane / cerebellum development / protein tetramerization / potassium ion transport / protein homooligomerization / 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: 3.2 Å | ||||||
Authors | Chi, G. / Qian, P. / Castro-Hartmann, P. / Venkaya, S. / Singh, N.K. / McKinley, G. / Mukhopadhyay, S.M.M. / Fernandez-Cid, A. / Pike, A.C.W. / Marsden, B. ...Chi, G. / Qian, P. / Castro-Hartmann, P. / Venkaya, S. / Singh, N.K. / McKinley, G. / Mukhopadhyay, S.M.M. / Fernandez-Cid, A. / Pike, A.C.W. / Marsden, B. / MacLean, E.M. / Sader, K. / Burgess-Brown, N.A. / Duerr, K.L. | ||||||
Funding support | United Kingdom, 1items
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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 |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7phl.cif.gz | 291.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7phl.ent.gz | 232.9 KB | Display | PDB format |
PDBx/mmJSON format | 7phl.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ph/7phl ftp://data.pdbj.org/pub/pdb/validation_reports/ph/7phl | HTTPS FTP |
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-Related structure data
Related structure data | 13419MC 7phhC 7phiC 7phkC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-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 | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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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 |
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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 |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 47.6 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||
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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: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 217788 / Symmetry type: POINT | ||||||||||||||||||||||||
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