+Open data
-Basic information
Entry | Database: PDB / ID: 8f1d | ||||||
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Title | Voltage-gated potassium channel Kv3.1 apo | ||||||
Components | Potassium voltage-gated channel subfamily C member 1 | ||||||
Keywords | TRANSPORT PROTEIN / ion channel / positive modulator / voltage gated / voltage gated potassium channel | ||||||
Function / homology | Function and homology information response to nerve growth factor / globus pallidus development / response to auditory stimulus / response to fibroblast growth factor / response to potassium ion / corpus callosum development / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / positive regulation of potassium ion transmembrane transport / delayed rectifier potassium channel activity / Voltage gated Potassium channels ...response to nerve growth factor / globus pallidus development / response to auditory stimulus / response to fibroblast growth factor / response to potassium ion / corpus callosum development / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / positive regulation of potassium ion transmembrane transport / delayed rectifier potassium channel activity / Voltage gated Potassium channels / response to light intensity / optic nerve development / neuronal cell body membrane / response to amine / action potential / kinesin binding / calyx of Held / voltage-gated potassium channel activity / axolemma / voltage-gated potassium channel complex / axon terminus / dendrite membrane / potassium ion transmembrane transport / 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: 2.94 Å | ||||||
Authors | Chen, Y. / Ishchenko, A. | ||||||
Funding support | United States, 1items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2023 Title: Identification, structural, and biophysical characterization of a positive modulator of human Kv3.1 channels. Authors: Yun-Ting Chen / Mee Ra Hong / Xin-Jun Zhang / James Kostas / Yuxing Li / Richard L Kraus / Vincent P Santarelli / Deping Wang / Yacob Gomez-Llorente / Alexei Brooun / Corey Strickland / ...Authors: Yun-Ting Chen / Mee Ra Hong / Xin-Jun Zhang / James Kostas / Yuxing Li / Richard L Kraus / Vincent P Santarelli / Deping Wang / Yacob Gomez-Llorente / Alexei Brooun / Corey Strickland / Stephen M Soisson / Daniel J Klein / Anthony T Ginnetti / Michael J Marino / Shawn J Stachel / Andrii Ishchenko / Abstract: Voltage-gated potassium channels (Kv) are tetrameric membrane proteins that provide a highly selective pathway for potassium ions (K) to diffuse across a hydrophobic cell membrane. These unique ...Voltage-gated potassium channels (Kv) are tetrameric membrane proteins that provide a highly selective pathway for potassium ions (K) to diffuse across a hydrophobic cell membrane. These unique voltage-gated cation channels detect changes in membrane potential and, upon activation, help to return the depolarized cell to a resting state during the repolarization stage of each action potential. The Kv3 family of potassium channels is characterized by a high activation potential and rapid kinetics, which play a crucial role for the fast-spiking neuronal phenotype. Mutations in the Kv3.1 channel have been shown to have implications in various neurological diseases like epilepsy and Alzheimer's disease. Moreover, disruptions in neuronal circuitry involving Kv3.1 have been correlated with negative symptoms of schizophrenia. Here, we report the discovery of a novel positive modulator of Kv3.1, investigate its biophysical properties, and determine the cryo-EM structure of the compound in complex with Kv3.1. Structural analysis reveals the molecular determinants of positive modulation in Kv3.1 channels by this class of compounds and provides additional opportunities for rational drug design for the treatment of associated neurological disorders. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8f1d.cif.gz | 331.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8f1d.ent.gz | 265 KB | Display | PDB format |
PDBx/mmJSON format | 8f1d.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8f1d_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 8f1d_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 8f1d_validation.xml.gz | 52.1 KB | Display | |
Data in CIF | 8f1d_validation.cif.gz | 75.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/f1/8f1d ftp://data.pdbj.org/pub/pdb/validation_reports/f1/8f1d | HTTPS FTP |
-Related structure data
Related structure data | 28795MC 8f1cC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 62745.266 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KCNC1 / Cell line (production host): Expi293, human-derived / Production host: Homo sapiens (human) / References: UniProt: P48547 #2: Chemical | ChemComp-ZN / #3: Chemical | ChemComp-CLR / #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: potassium voltage-gated channel / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Value: 0.24 MDa / Experimental value: YES |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: Expi293, human-derived / Plasmid: Mammalian expression vector EGFP-MCS-pcDNA3.1 |
Buffer solution | pH: 8 |
Specimen | Conc.: 3.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 42.5 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1937733 | ||||||||||||||||||||||||
Symmetry | Point symmetry: C4 (4 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.94 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 140000 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL | ||||||||||||||||||||||||
Refine LS restraints |
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