+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of human Kv1.3 with Fab-ShK fusion | |||||||||
![]() | Human Kv1.3 with Fab-ShK | |||||||||
![]() |
| |||||||||
Function / homology | ![]() corpus callosum development / voltage-gated monoatomic ion channel activity / Voltage gated Potassium channels / delayed rectifier potassium channel activity / optic nerve development / outward rectifier potassium channel activity / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Meyerson JR / Selvakumar P / Smider V / Huang R | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 307.3 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 12.5 KB 12.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 15.8 KB | Display | ![]() |
Images | ![]() | 94.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7ssvMC ![]() 7ssxC ![]() 7ssyC ![]() 7sszC ![]() 8dflC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
EM raw data | ![]() Data #1: Human Kv1.3 ShK-Fab dataset [micrographs - multiframe]) |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Human Kv1.3 with Fab-ShK | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.852 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-
Sample components
-Entire : Kv1.3 with Fab-ShK
Entire | Name: Kv1.3 with Fab-ShK |
---|---|
Components |
|
-Supramolecule #1: Kv1.3 with Fab-ShK
Supramolecule | Name: Kv1.3 with Fab-ShK / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
---|---|
Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Potassium voltage-gated channel subfamily A member 3,Green fluore...
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 |
---|---|
Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 95.0185 KDa |
Recombinant expression | Organism: ![]() ![]() |
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 |
-Macromolecule #2: Fab-ShK fusion, heavy chain
Macromolecule | Name: Fab-ShK fusion, heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: unidentified (others) |
Molecular weight | Theoretical: 29.417229 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QVQLREWGAG LLKPSETLSL TCAVYGGSFS DKYWSWIRQP PGKGLEWIGS INHSGSTNYN PSLKSRVTIS VDTSKNQFSL KLSSVTAAD TAVYYCTSVH QETKKYQSRS CIDTIPKSRC TAFQCKHSMK YRLSFCRKTC GTCSYTYNYE WHVDVWGQGL L VTVSSAST ...String: QVQLREWGAG LLKPSETLSL TCAVYGGSFS DKYWSWIRQP PGKGLEWIGS INHSGSTNYN PSLKSRVTIS VDTSKNQFSL KLSSVTAAD TAVYYCTSVH QETKKYQSRS CIDTIPKSRC TAFQCKHSMK YRLSFCRKTC GTCSYTYNYE WHVDVWGQGL L VTVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SS LGTQTYI CNVNHKPSNT KVDKKVEPKS CDK |
-Macromolecule #3: Fab-ShK fusion, light chain
Macromolecule | Name: Fab-ShK fusion, light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: unidentified (others) |
Molecular weight | Theoretical: 22.524752 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QAVLNQPSSV SGSLGQKVTI SCSGSSSNIG NNYVSWYQQL PGTAPKLLIY GDTKRPSGIP DRFSGSKSGT SATLGITGLQ TGDEADYYC ASAEDSSSNA VFGSGTTLTV LGQPKAAPSV TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADSSPV K AGVETTTP ...String: QAVLNQPSSV SGSLGQKVTI SCSGSSSNIG NNYVSWYQQL PGTAPKLLIY GDTKRPSGIP DRFSGSKSGT SATLGITGLQ TGDEADYYC ASAEDSSSNA VFGSGTTLTV LGQPKAAPSV TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADSSPV K AGVETTTP SKQSNNKYAA SSYLSLTPEQ WKSHRSYSCQ VTHEGSTVEK TVAPTECS |
-Macromolecule #4: POTASSIUM ION
Macromolecule | Name: POTASSIUM ION / type: ligand / ID: 4 / Number of copies: 3 / Formula: K |
---|---|
Molecular weight | Theoretical: 39.098 Da |
-Experimental details
-Structure determination
Method | ![]() |
---|---|
![]() | ![]() |
Aggregation state | particle |
-
Sample preparation
Buffer | pH: 7.5 |
---|---|
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 54.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |