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Open data
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Basic information
Entry | Database: PDB / ID: 7ssz | ||||||
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Title | Structure of human Kv1.3 with A0194009G09 nanobodies | ||||||
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![]() | IMMUNE SYSTEM / ion channel | ||||||
Function / homology | ![]() corpus callosum development / voltage-gated monoatomic ion channel activity / Voltage gated Potassium channels / outward rectifier potassium channel activity / delayed rectifier potassium channel activity / optic nerve development / action potential / calyx of Held / voltage-gated potassium channel complex / potassium ion transmembrane transport ...corpus callosum development / voltage-gated monoatomic ion channel activity / Voltage gated Potassium channels / outward rectifier potassium channel activity / delayed rectifier potassium channel activity / optic nerve development / action potential / calyx of Held / voltage-gated potassium channel complex / potassium ion transmembrane transport / bioluminescence / generation of precursor metabolites and energy / potassium ion transport / protein homooligomerization / presynaptic membrane / postsynaptic membrane / membrane raft / axon / glutamatergic synapse / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() synthetic construct (others) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.25 Å | ||||||
![]() | Meyerson, J.R. / Selvakumar, P. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structures of the T cell potassium channel Kv1.3 with immunoglobulin modulators. Authors: Purushotham Selvakumar / Ana I Fernández-Mariño / Nandish Khanra / Changhao He / Alice J Paquette / Bing Wang / Ruiqi Huang / Vaughn V Smider / William J Rice / Kenton J Swartz / Joel R Meyerson / ![]() Abstract: The Kv1.3 potassium channel is expressed abundantly on activated T cells and mediates the cellular immune response. This role has made the channel a target for therapeutic immunomodulation to block ...The Kv1.3 potassium channel is expressed abundantly on activated T cells and mediates the cellular immune response. This role has made the channel a target for therapeutic immunomodulation to block its activity and suppress T cell activation. Here, we report structures of human Kv1.3 alone, with a nanobody inhibitor, and with an antibody-toxin fusion blocker. Rather than block the channel directly, four copies of the nanobody bind the tetramer's voltage sensing domains and the pore domain to induce an inactive pore conformation. In contrast, the antibody-toxin fusion docks its toxin domain at the extracellular mouth of the channel to insert a critical lysine into the pore. The lysine stabilizes an active conformation of the pore yet blocks ion permeation. This study visualizes Kv1.3 pore dynamics, defines two distinct mechanisms to suppress Kv1.3 channel activity with exogenous inhibitors, and provides a framework to aid development of emerging T cell immunotherapies. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 366.3 KB | Display | ![]() |
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PDB format | ![]() | 285.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 25417MC ![]() 7ssvC ![]() 7ssxC ![]() 7ssyC ![]() 8dflC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
EM raw data | ![]() Data #1: Human Kv1.3 nanobody dataset 1 [micrographs - multiframe] Data #2: Human Kv1.3 nanobody dataset 2 [micrographs - multiframe]) |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 95018.500 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: KCNA3, HGK5, GFP / Production host: ![]() #2: Antibody | Mass: 13849.449 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: ![]() ![]() #3: Chemical | 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 |
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Sample preparation
Component | Name: Kv1.3 with nanobody A0194009G09 / Type: COMPLEX / Entity ID: #1-#2 / Source: MULTIPLE SOURCES |
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Molecular weight | Units: MEGADALTONS |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 54 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.25 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 123722 / Symmetry type: POINT |