+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-25416 | |||||||||
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Title | Structure of human Kv1.3 | |||||||||
Map data | Human Kv1.3 | |||||||||
Sample |
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Keywords | ion channel / IMMUNE SYSTEM | |||||||||
Function / homology | Function and homology information corpus callosum development / voltage-gated monoatomic ion channel activity / delayed rectifier potassium channel activity / Voltage gated Potassium channels / outward 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 / delayed rectifier potassium channel activity / Voltage gated Potassium channels / outward 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 | Homo sapiens (human) / Aequorea victoria (jellyfish) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.89 Å | |||||||||
Authors | Meyerson JR / Selvakumar P | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nat Commun / Year: 2022 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. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_25416.map.gz | 117.7 MB | EMDB map data format | |
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Header (meta data) | emd-25416-v30.xml emd-25416.xml | 14.2 KB 14.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_25416_fsc.xml | 11.5 KB | Display | FSC data file |
Images | emd_25416.png | 108.1 KB | ||
Filedesc metadata | emd-25416.cif.gz | 5.6 KB | ||
Others | emd_25416_additional_1.map.gz emd_25416_additional_2.map.gz | 4.4 MB 4.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-25416 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-25416 | HTTPS FTP |
-Validation report
Summary document | emd_25416_validation.pdf.gz | 511.8 KB | Display | EMDB validaton report |
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Full document | emd_25416_full_validation.pdf.gz | 511.4 KB | Display | |
Data in XML | emd_25416_validation.xml.gz | 12 KB | Display | |
Data in CIF | emd_25416_validation.cif.gz | 16 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25416 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25416 | HTTPS FTP |
-Related structure data
Related structure data | 7ssxMC 7ssyMC 7ssvC 7sszC 8dflC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
EM raw data | EMPIAR-11071 (Title: Human Kv1.3 / Data size: 1.4 TB / Data #1: Human Kv1.3 dataset 1 [micrographs - multiframe] / Data #2: Human Kv1.3 dataset 2 [micrographs - multiframe] / Data #3: Human Kv1.3 dataset 3 [micrographs - multiframe]) |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_25416.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Human Kv1.3 | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.852 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Human Kv1.3 (single subunit, D1 conformation)
File | emd_25416_additional_1.map | ||||||||||||
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Annotation | Human Kv1.3 (single subunit, D1 conformation) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Human Kv1.3 (single subunit, D2 conformation)
File | emd_25416_additional_2.map | ||||||||||||
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Annotation | Human Kv1.3 (single subunit, D2 conformation) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Kv1.3
Entire | Name: Kv1.3 |
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Components |
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-Supramolecule #1: Kv1.3
Supramolecule | Name: Kv1.3 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Potassium voltage-gated channel subfamily A member 3, Green fluor...
Macromolecule | Name: Potassium voltage-gated channel subfamily A member 3, Green fluorescent protein fusion type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Aequorea victoria (jellyfish) |
Molecular weight | Theoretical: 95.0185 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: 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 SGFSSIPDAF 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 |
-Macromolecule #2: POTASSIUM ION
Macromolecule | Name: POTASSIUM ION / type: ligand / ID: 2 / Number of copies: 3 / 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
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-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: 54.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |