+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-28795 | |||||||||
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Title | Voltage-gated potassium channel Kv3.1 apo | |||||||||
Map data | ||||||||||
Sample |
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Keywords | ion channel / positive modulator / voltage gated / voltage gated potassium channel / TRANSPORT PROTEIN | |||||||||
Function / homology | Function and homology information response to nerve growth factor / globus pallidus development / response to potassium ion / response to auditory stimulus / response to fibroblast growth factor / 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 / response to light intensity ...response to nerve growth factor / globus pallidus development / response to potassium ion / response to auditory stimulus / response to fibroblast growth factor / 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 / response to light intensity / Voltage gated Potassium channels / optic nerve development / action potential / neuronal cell body membrane / response to amine / kinesin binding / voltage-gated potassium channel activity / 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 | single particle reconstruction / cryo EM / Resolution: 2.94 Å | |||||||||
Authors | Chen Y / Ishchenko A | |||||||||
Funding support | United States, 1 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_28795.map.gz | 96.7 MB | EMDB map data format | |
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Header (meta data) | emd-28795-v30.xml emd-28795.xml | 16.8 KB 16.8 KB | Display Display | EMDB header |
Images | emd_28795.png | 122.7 KB | ||
Filedesc metadata | emd-28795.cif.gz | 6.1 KB | ||
Others | emd_28795_half_map_1.map.gz emd_28795_half_map_2.map.gz | 94.7 MB 94.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-28795 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-28795 | HTTPS FTP |
-Validation report
Summary document | emd_28795_validation.pdf.gz | 848.8 KB | Display | EMDB validaton report |
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Full document | emd_28795_full_validation.pdf.gz | 848.4 KB | Display | |
Data in XML | emd_28795_validation.xml.gz | 13.2 KB | Display | |
Data in CIF | emd_28795_validation.cif.gz | 15.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28795 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28795 | HTTPS FTP |
-Related structure data
Related structure data | 8f1dMC 8f1cC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_28795.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.84 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_28795_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_28795_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : potassium voltage-gated channel
Entire | Name: potassium voltage-gated channel |
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Components |
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-Supramolecule #1: potassium voltage-gated channel
Supramolecule | Name: potassium voltage-gated channel / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 240 KDa |
-Macromolecule #1: Potassium voltage-gated channel subfamily C member 1
Macromolecule | Name: Potassium voltage-gated channel subfamily C member 1 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 62.745266 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MADYKDHDGD YKDHDIDYKD DDDKLEVLFQ GPGSMGQGDE SERIVINVGG TRHQTYRSTL RTLPGTRLAW LAEPDAHSHF DYDPRADEF FFDRHPGVFA HILNYYRTGK LHCPADVCGP LYEEELAFWG IDETDVEPCC WMTYRQHRDA EEALDSFGGA P LDNSADDA ...String: MADYKDHDGD YKDHDIDYKD DDDKLEVLFQ GPGSMGQGDE SERIVINVGG TRHQTYRSTL RTLPGTRLAW LAEPDAHSHF DYDPRADEF FFDRHPGVFA HILNYYRTGK LHCPADVCGP LYEEELAFWG IDETDVEPCC WMTYRQHRDA EEALDSFGGA P LDNSADDA DADGPGDSGD GEDELEMTKR LALSDSPDGR PGGFWRRWQP RIWALFEDPY SSRYARYVAF ASLFFILVSI TT FCLETHE RFNPIVNKTE IENVRNGTQV RYYREAETEA FLTYIEGVCV VWFTFEFLMR VIFCPNKVEF IKNSLNIIDF VAI LPFYLE VGLSGLSSKA AKDVLGFLRV VRFVRILRIF KLTRHFVGLR VLGHTLRAST NEFLLLIIFL ALGVLIFATM IYYA ERIGA QPNDPSASEH THFKNIPIGF WWAVVTMTTL GYGDMYPQTW SGMLVGALCA LAGVLTIAMP VPVIVNNFGM YYSLA MAKQ KLPKKKKKHI PRPPQLGSPN YCKSVVNSPH HSTQSDTCPL AQEEILEINR AGRKPLRGMS ILEVLFQG UniProtKB: Voltage-gated potassium channel KCNC1 |
-Macromolecule #2: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 2 / Number of copies: 4 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Macromolecule #3: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 3 / Number of copies: 4 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ChemComp-CLR: |
-Macromolecule #4: POTASSIUM ION
Macromolecule | Name: POTASSIUM ION / type: ligand / ID: 4 / Number of copies: 4 / Formula: K |
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Molecular weight | Theoretical: 39.098 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 3.2 mg/mL |
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Buffer | pH: 8 |
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 3 sec. |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 42.5 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Protocol: AB INITIO MODEL |
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Output model | PDB-8f1d: |