+
Open data
-
Basic information
| Entry | Database: PDB / ID: 9ei0 | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Title | Human Kv1.3 mutant - G427H with A0194009G09 nanobodies | |||||||||||||||||||||||||||
Components |
| |||||||||||||||||||||||||||
Keywords | IMMUNE SYSTEM / Voltage-gated Potassium channel | |||||||||||||||||||||||||||
| Function / homology | Function and homology informationvoltage-gated monoatomic ion channel activity / delayed rectifier potassium channel activity / Voltage gated Potassium channels / action potential / potassium ion transport / voltage-gated potassium channel activity / voltage-gated potassium channel complex / potassium ion transmembrane transport / bioluminescence / generation of precursor metabolites and energy ...voltage-gated monoatomic ion channel activity / delayed rectifier potassium channel activity / Voltage gated Potassium channels / action potential / potassium ion transport / voltage-gated potassium channel activity / voltage-gated potassium channel complex / potassium ion transmembrane transport / bioluminescence / generation of precursor metabolites and energy / protein homooligomerization / axon / perinuclear region of cytoplasm / membrane / plasma membrane Similarity search - Function | |||||||||||||||||||||||||||
| Biological species | Homo sapiens (human)![]() | |||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.91 Å | |||||||||||||||||||||||||||
Authors | Selvakumar, P. / Swartz, K.J. | |||||||||||||||||||||||||||
| Funding support | United States, 1items
| |||||||||||||||||||||||||||
Citation | Journal: Nat Commun / Year: 2026Title: Nanobody regulation of C-type inactivation in Kv1.3 channels. Authors: Purushotham Selvakumar / Kenton J Swartz / Ana I Fernández-Mariño / ![]() Abstract: Nanobodies are powerful tools for modulating ion channels for mechanistic investigations and developing new therapeutics. The Kv1.3 channel is highly expressed in T-lymphocytes where it promotes ...Nanobodies are powerful tools for modulating ion channels for mechanistic investigations and developing new therapeutics. The Kv1.3 channel is highly expressed in T-lymphocytes where it promotes sustained T-cell activation, its expression is elevated in autoimmune disorders and inhibitory nanobodies are immunosuppressive. The A019400G09 nanobody (NB1.3) binds to the external surface of Kv1.3 and inhibits the channel by promoting slow C-type inactivation of the ion selectivity filter. Here we explore the mechanism by which NB1.3 promotes inactivation by determining a series of cryo-EM structures of Kv1.3 and mutating the interface between NB1.3 and the channel. Our results reveal that interaction of NB1.3 with both the S1-S4 voltage-sensing domain and the turret within the pore domain are required to promote inactivation. We also identify a network of interacting hydrophobic residues linking the turret to the ion selectivity filter that stabilizes the conducting state and mediate the actions of NB1.3. These findings provide a foundation for developing therapeutics targeting Kv1.3 channels and exploring how nanobodies can interact with other tetrameric cation channels to modulate their activity. | |||||||||||||||||||||||||||
| History |
|
-
Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
|---|
-
Downloads & links
-
Download
| PDBx/mmCIF format | 9ei0.cif.gz | 411.2 KB | Display | PDBx/mmCIF format |
|---|---|---|---|---|
| PDB format | pdb9ei0.ent.gz | 316.3 KB | Display | PDB format |
| PDBx/mmJSON format | 9ei0.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ei/9ei0 ftp://data.pdbj.org/pub/pdb/validation_reports/ei/9ei0 | HTTPS FTP |
|---|
-Related structure data
| Related structure data | ![]() 48072MC ![]() 9eefC M: map data used to model this data C: citing same article ( |
|---|---|
| Similar structure data | Similarity search - Function & homology F&H Search |
-
Links
-
Assembly
| Deposited unit | ![]()
|
|---|---|
| 1 |
|
-
Components
| #1: Protein | Mass: 95099.594 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KCNA3, HGK5, GFP / Production host: Homo sapiens (human) / References: UniProt: P22001, UniProt: P42212#2: Antibody | Mass: 13849.449 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #3: Chemical | ChemComp-K / Has ligand of interest | N | Has protein modification | Y | |
|---|
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
|---|---|
| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
| Component | Name: Kv1.3-G427H mutant protein fused with mVenus and A0194009G09 nanobodies Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
|---|---|
| Molecular weight | Experimental value: NO |
| Source (natural) | Organism: ![]() |
| Source (recombinant) | Organism: Homo sapiens (human) |
| 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 |
|---|---|
| Microscopy | Model: TFS KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm |
| Image recording | Electron dose: 51.6 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-
Processing
| EM software |
| ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||
| Symmetry | Point symmetry: C4 (4 fold cyclic) | ||||||||||||||||
| 3D reconstruction | Resolution: 2.91 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 259382 / Symmetry type: POINT |
Movie
Controller
About Yorodumi




Homo sapiens (human)

United States, 1items
Citation



PDBj














FIELD EMISSION GUN