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Yorodumi- PDB-7wf3: Composite map of human Kv1.3 channel in apo state with beta subunits -
+Open data
-Basic information
Entry | Database: PDB / ID: 7wf3 | |||||||||
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Title | Composite map of human Kv1.3 channel in apo state with beta subunits | |||||||||
Components |
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Keywords | MEMBRANE PROTEIN / Ion channel / Kv channel / Potassium channel / Peptide toxin / ShK / Dalazatide / Selectivity filter / Molecular dynamics simulation | |||||||||
Function / homology | Function and homology information pinceau fiber / regulation of action potential / NADPH oxidation / regulation of protein localization to cell surface / corpus callosum development / voltage-gated monoatomic ion channel activity / aldo-keto reductase (NADPH) activity / Voltage gated Potassium channels / outward rectifier potassium channel activity / juxtaparanode region of axon ...pinceau fiber / regulation of action potential / NADPH oxidation / regulation of protein localization to cell surface / corpus callosum development / voltage-gated monoatomic ion channel activity / aldo-keto reductase (NADPH) activity / Voltage gated Potassium channels / outward rectifier potassium channel activity / juxtaparanode region of axon / regulation of potassium ion transmembrane transport / Oxidoreductases; Acting on the CH-OH group of donors; With NAD+ or NADP+ as acceptor / delayed rectifier potassium channel activity / optic nerve development / voltage-gated potassium channel activity / action potential / calyx of Held / tertiary granule membrane / potassium channel regulator activity / specific granule membrane / voltage-gated potassium channel complex / potassium ion transmembrane transport / potassium ion transport / protein homooligomerization / cytoplasmic side of plasma membrane / presynaptic membrane / postsynaptic membrane / transmembrane transporter binding / cytoskeleton / membrane raft / axon / glutamatergic synapse / synapse / Neutrophil degranulation / membrane / plasma membrane / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Tyagi, A. / Ahmed, T. / Jian, S. / Bajaj, S. / Ong, S.T. / Goay, S.S.M. / Zhao, Y. / Vorobyov, I. / Tian, C. / Chandy, K.G. / Bhushan, S. | |||||||||
Funding support | Singapore, 1items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2022 Title: Rearrangement of a unique Kv1.3 selectivity filter conformation upon binding of a drug. Authors: Anu Tyagi / Tofayel Ahmed / Shi Jian / Saumya Bajaj / Seow Theng Ong / Stephanie Shee Min Goay / Yue Zhao / Igor Vorobyov / Changlin Tian / K George Chandy / Shashi Bhushan / Abstract: We report two structures of the human voltage-gated potassium channel (Kv) Kv1.3 in immune cells alone (apo-Kv1.3) and bound to an immunomodulatory drug called dalazatide (dalazatide-Kv1.3). Both the ...We report two structures of the human voltage-gated potassium channel (Kv) Kv1.3 in immune cells alone (apo-Kv1.3) and bound to an immunomodulatory drug called dalazatide (dalazatide-Kv1.3). Both the apo-Kv1.3 and dalazatide-Kv1.3 structures are in an activated state based on their depolarized voltage sensor and open inner gate. In apo-Kv1.3, the aromatic residue in the signature sequence (Y447) adopts a position that diverges 11 Å from other K channels. The outer pore is significantly rearranged, causing widening of the selectivity filter and perturbation of ion binding within the filter. This conformation is stabilized by a network of intrasubunit hydrogen bonds. In dalazatide-Kv1.3, binding of dalazatide to the channel's outer vestibule narrows the selectivity filter, Y447 occupies a position seen in other K channels, and this conformation is stabilized by a network of intersubunit hydrogen bonds. These remarkable rearrangements in the selectivity filter underlie Kv1.3's transition into the drug-blocked state. | |||||||||
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 | 7wf3.cif.gz | 481.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7wf3.ent.gz | 406.1 KB | Display | PDB format |
PDBx/mmJSON format | 7wf3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7wf3_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 7wf3_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 7wf3_validation.xml.gz | 72.4 KB | Display | |
Data in CIF | 7wf3_validation.cif.gz | 111.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wf/7wf3 ftp://data.pdbj.org/pub/pdb/validation_reports/wf/7wf3 | HTTPS FTP |
-Related structure data
Related structure data | 32459MC 7wf4C 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
-Potassium voltage-gated channel subfamily A member ... , 2 types, 8 molecules BDFHJNOP
#1: Protein | Mass: 31747.734 Da / Num. of mol.: 4 / Fragment: TM domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KCNA3, HGK5 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P22001 #3: Protein | Mass: 12777.475 Da / Num. of mol.: 4 / Fragment: T1 domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KCNA3, HGK5 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P22001 |
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-Protein , 1 types, 4 molecules CGIM
#2: Protein | Mass: 36704.254 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KCNAB2, KCNA2B, KCNK2 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: Q13303, Oxidoreductases; Acting on the CH-OH group of donors; With NAD+ or NADP+ as acceptor |
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-Non-polymers , 3 types, 124 molecules
#4: Chemical | ChemComp-K / #5: Chemical | ChemComp-NAP / #6: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | Y |
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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
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Molecular weight |
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Specimen | 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 / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 65 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 177130 Details: The above mentioned 3.4 Ang resolution was obtained for TM domain after application of C4 symmetry. The soluble domain map (another map deposited here) was resolved to 2.9 Ang. Symmetry type: POINT |