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- EMDB-48072: Human Kv1.3 mutant - G427H with A0194009G09 nanobodies -

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Basic information

Entry
Database: EMDB / ID: EMD-48072
TitleHuman Kv1.3 mutant - G427H with A0194009G09 nanobodies
Map dataHuman Kv1.3 mutant - G427H with A0194009G09 nanobodies
Sample
  • Complex: Kv1.3-G427H mutant protein fused with mVenus and A0194009G09 nanobodies
    • Protein or peptide: Potassium voltage-gated channel subfamily A member 3,Green fluorescent protein
    • Protein or peptide: A0194009G09 nanobody
  • Ligand: POTASSIUM ION
KeywordsVoltage-gated Potassium channel / IMMUNE SYSTEM
Function / homology
Function and homology information


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 ...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
Potassium channel, voltage dependent, Kv1.3 / Potassium channel, voltage dependent, Kv1 / Potassium channel, voltage dependent, Kv / Potassium channel tetramerisation-type BTB domain / BTB/POZ domain / Voltage-gated potassium channel / Broad-Complex, Tramtrack and Bric a brac / BTB/POZ domain / Voltage-dependent channel domain superfamily / Green fluorescent protein, GFP ...Potassium channel, voltage dependent, Kv1.3 / Potassium channel, voltage dependent, Kv1 / Potassium channel, voltage dependent, Kv / Potassium channel tetramerisation-type BTB domain / BTB/POZ domain / Voltage-gated potassium channel / Broad-Complex, Tramtrack and Bric a brac / BTB/POZ domain / Voltage-dependent channel domain superfamily / Green fluorescent protein, GFP / Green fluorescent protein-related / Green fluorescent protein / Green fluorescent protein / SKP1/BTB/POZ domain superfamily / Ion transport domain / Ion transport protein
Similarity search - Domain/homology
Potassium voltage-gated channel subfamily A member 3 / Green fluorescent protein
Similarity search - Component
Biological speciesAequorea victoria (jellyfish) / Homo sapiens (human) / Lama glama (llama)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.91 Å
AuthorsSelvakumar P / Swartz KJ
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)NS 002945-28 United States
CitationJournal: Nat Commun / Year: 2026
Title: 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
DepositionNov 25, 2024-
Header (metadata) releaseDec 3, 2025-
Map releaseDec 3, 2025-
UpdateSep 16, 2026-
Current statusSep 16, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_48072.png

Downloads & links

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Map

FileDownload / File: emd_48072.map.gz / Format: CCP4 / Size: 274.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationHuman Kv1.3 mutant - G427H with A0194009G09 nanobodies
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 416 pix.
= 345.28 Å		0.83 Å/pix.
x 416 pix.
= 345.28 Å		0.83 Å/pix.
x 416 pix.
= 345.28 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.2
Minimum - Maximum-1.9145446 - 2.5752833
Average (Standard dev.)0.0011471364 (±0.033316344)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions416416416
Spacing416416416
CellA=B=C: 345.28 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_48072_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Half Map B

Fileemd_48072_half_map_1.map
AnnotationHalf Map B
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Half Map A

Fileemd_48072_half_map_2.map
AnnotationHalf Map A
Projections & Slices
AxesZYX

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Slices (1/2)
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Histogram

Histogram (log scale)

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Sample components

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Entire : Kv1.3-G427H mutant protein fused with mVenus and A0194009G09 nano...

EntireName: Kv1.3-G427H mutant protein fused with mVenus and A0194009G09 nanobodies
Components
  • Complex: Kv1.3-G427H mutant protein fused with mVenus and A0194009G09 nanobodies
    • Protein or peptide: Potassium voltage-gated channel subfamily A member 3,Green fluorescent protein
    • Protein or peptide: A0194009G09 nanobody
  • Ligand: POTASSIUM ION

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Supramolecule #1: Kv1.3-G427H mutant protein fused with mVenus and A0194009G09 nano...

SupramoleculeName: Kv1.3-G427H mutant protein fused with mVenus and A0194009G09 nanobodies
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Aequorea victoria (jellyfish)

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Macromolecule #1: Potassium voltage-gated channel subfamily A member 3,Green fluore...

MacromoleculeName: Potassium voltage-gated channel subfamily A member 3,Green fluorescent protein
type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 95.099594 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MDERLSLLRS PPPPSARHRA HPPQRPASSG GAHTLVNHGY AEPAAGRELP PDMTVVPGDH LLEPEVADGG GAPPQGGCGG GGCDRYEPL PPSLPAAGEQ DCCGERVVIN ISGLRFETQL KTLCQFPETL LGDPKRRMRY FDPLRNEYFF DRNRPSFDAI L YYYQSGGR ...String:
MDERLSLLRS PPPPSARHRA HPPQRPASSG GAHTLVNHGY AEPAAGRELP PDMTVVPGDH LLEPEVADGG GAPPQGGCGG GGCDRYEPL PPSLPAAGEQ DCCGERVVIN ISGLRFETQL KTLCQFPETL LGDPKRRMRY FDPLRNEYFF DRNRPSFDAI L YYYQSGGR IRRPVNVPID IFSEEIRFYQ LGEEAMEKFR EDEGFLREEE RPLPRRDFQR QVWLLFEYPE SSGPARGIAI VS VLVILIS IVIFCLETLP EFRDEKDYPA STSQDSFEAA GNSTSGSRAG ASSFSDPFFV VETLCIIWFS FELLVRFFAC PSK ATFSRN IMNLIDIVAI IPYFITLGTE LAERQGNGQQ AMSLAILRVI RLVRVFRIFK LSRHSKGLQI LGQTLKASMR ELGL LIFFL FIGVILFSSA VYFAEADDPT SHFSSIPDAF WWAVVTMTTV GYGDMHPVTI GGKIVGSLCA IAGVLTIALP VPVIV SNFN YFYHRETEGE EQSQYMHVGS CQHLSSSAEE LRKARSNSTL SKSEYMVIEE GGMNHSAFPQ TPFKTGNSTA TCTTNN NPN SCVNIKKIFT DVSLEVLFQG PAAAMVSKGE ELFTGVVPIL VELDGDVNGH KFSVSGEGEG DATYGKLTLK LICTTGK LP VPWPTLVTTL GYGLQCFARY PDHMKQHDFF KSAMPEGYVQ ERTIFFKDDG NYKTRAEVKF EGDTLVNRIE LKGIDFKE D GNILGHKLEY NYNSHNVYIT ADKQKNGIKA NFKIRHNIED GGVQLADHYQ QNTPIGDGPV LLPDNHYLSY QSKLSKDPN EKRDHMVLLE FVTAAGITLG MDELYKSAWS HPQFEKGGGS GGGSGGGSWS HPQFEK

UniProtKB: Potassium voltage-gated channel subfamily A member 3, Green fluorescent protein

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Macromolecule #2: A0194009G09 nanobody

MacromoleculeName: A0194009G09 nanobody / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Lama glama (llama)
Molecular weightTheoretical: 13.849449 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
MEVQLVESGG GLVQAGGSLG LSCSASGLLF SRNSAGWYRQ APGKQREFVA RIRMGGSINY ADTVKGRFTI SRDNAKNTVY LQMNSLKPE DTAVYYCSSW RTGFYEYWGQ GTLVTVSSAA AHHHHHH

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Macromolecule #3: POTASSIUM ION

MacromoleculeName: POTASSIUM ION / type: ligand / ID: 3 / Number of copies: 4 / Formula: K
Molecular weightTheoretical: 39.098 Da

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 51.6 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE / Details: Abinitio
Final reconstructionApplied symmetry - Point group: C4 (4 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 2.91 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 259382
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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