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Yorodumi- EMDB-32459: Composite map of human Kv1.3 channel in apo state with beta subunits -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-32459 | |||||||||
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Title | Composite map of human Kv1.3 channel in apo state with beta subunits | |||||||||
Map data | Composite map of human Kv1.3 channel with beta subunits | |||||||||
Sample |
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Function / homology | Function and homology information pinceau fiber / regulation of action potential / NADPH oxidation / regulation of protein localization to cell surface / corpus callosum development / voltage-gated monoatomic ion channel activity / aldo-keto reductase (NADPH) activity / Voltage gated Potassium channels / outward rectifier potassium channel activity / juxtaparanode region of axon ...pinceau fiber / regulation of action potential / NADPH oxidation / regulation of protein localization to cell surface / corpus callosum development / voltage-gated monoatomic ion channel activity / aldo-keto reductase (NADPH) activity / Voltage gated Potassium channels / outward rectifier potassium channel activity / juxtaparanode region of axon / regulation of potassium ion transmembrane transport / Oxidoreductases; Acting on the CH-OH group of donors; With NAD+ or NADP+ as acceptor / delayed rectifier potassium channel activity / optic nerve development / voltage-gated potassium channel activity / action potential / calyx of Held / tertiary granule membrane / potassium channel regulator activity / specific granule membrane / voltage-gated potassium channel complex / potassium ion transmembrane transport / potassium ion transport / protein homooligomerization / cytoplasmic side of plasma membrane / presynaptic membrane / postsynaptic membrane / transmembrane transporter binding / cytoskeleton / membrane raft / axon / glutamatergic synapse / synapse / Neutrophil degranulation / membrane / plasma membrane / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Tyagi A / Ahmed T / Jian S / Bajaj S / Ong ST / Goay SSM / Zhao Y / Vorobyov I / Tian C / Chandy KG / Bhushan S | |||||||||
Funding support | Singapore, 1 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2022 Title: Rearrangement of a unique Kv1.3 selectivity filter conformation upon binding of a drug. Authors: Anu Tyagi / Tofayel Ahmed / Shi Jian / Saumya Bajaj / Seow Theng Ong / Stephanie Shee Min Goay / Yue Zhao / Igor Vorobyov / Changlin Tian / K George Chandy / Shashi Bhushan / Abstract: We report two structures of the human voltage-gated potassium channel (Kv) Kv1.3 in immune cells alone (apo-Kv1.3) and bound to an immunomodulatory drug called dalazatide (dalazatide-Kv1.3). Both the ...We report two structures of the human voltage-gated potassium channel (Kv) Kv1.3 in immune cells alone (apo-Kv1.3) and bound to an immunomodulatory drug called dalazatide (dalazatide-Kv1.3). Both the apo-Kv1.3 and dalazatide-Kv1.3 structures are in an activated state based on their depolarized voltage sensor and open inner gate. In apo-Kv1.3, the aromatic residue in the signature sequence (Y447) adopts a position that diverges 11 Å from other K channels. The outer pore is significantly rearranged, causing widening of the selectivity filter and perturbation of ion binding within the filter. This conformation is stabilized by a network of intrasubunit hydrogen bonds. In dalazatide-Kv1.3, binding of dalazatide to the channel's outer vestibule narrows the selectivity filter, Y447 occupies a position seen in other K channels, and this conformation is stabilized by a network of intersubunit hydrogen bonds. These remarkable rearrangements in the selectivity filter underlie Kv1.3's transition into the drug-blocked state. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_32459.map.gz | 227 MB | EMDB map data format | |
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Header (meta data) | emd-32459-v30.xml emd-32459.xml | 15.4 KB 15.4 KB | Display Display | EMDB header |
Images | emd_32459.png | 119.3 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-32459 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32459 | HTTPS FTP |
-Validation report
Summary document | emd_32459_validation.pdf.gz | 428.1 KB | Display | EMDB validaton report |
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Full document | emd_32459_full_validation.pdf.gz | 427.7 KB | Display | |
Data in XML | emd_32459_validation.xml.gz | 7.7 KB | Display | |
Data in CIF | emd_32459_validation.cif.gz | 8.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32459 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32459 | HTTPS FTP |
-Related structure data
Related structure data | 7wf3MC 7wf4C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_32459.map.gz / Format: CCP4 / Size: 282.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Composite map of human Kv1.3 channel with beta subunits | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.858 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Composite map of human Kv1.3 channel in apo state with beta subunits
Entire | Name: Composite map of human Kv1.3 channel in apo state with beta subunits |
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Components |
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-Supramolecule #1: Composite map of human Kv1.3 channel in apo state with beta subunits
Supramolecule | Name: Composite map of human Kv1.3 channel in apo state with beta subunits type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera (butterflies/moths) |
-Supramolecule #2: TM domain focused map of human Kv1.3
Supramolecule | Name: TM domain focused map of human Kv1.3 / type: complex / Chimera: Yes / ID: 2 / Parent: 1 / Macromolecule list: #3 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera (butterflies/moths) |
-Supramolecule #3: Soluble domain focused map of human Kv1.3
Supramolecule | Name: Soluble domain focused map of human Kv1.3 / type: complex / Chimera: Yes / ID: 3 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera (butterflies/moths) |
-Macromolecule #1: Potassium voltage-gated channel subfamily A member 3
Macromolecule | Name: Potassium voltage-gated channel subfamily A member 3 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 31.747734 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: ERPLPRRDFQ RQVWLLFEYP ESSGPARGIA IVSVLVILIS IVIFCLETLP EFRDEKDYPA STSQDSFEAA GNSTSGSRAG ASSFSDPFF VVETLCIIWF SFELLVRFFA CPSKATFSRN IMNLIDIVAI IPYFITLGTE LAERQGNGQQ AMSLAILRVI R LVRVFRIF ...String: ERPLPRRDFQ RQVWLLFEYP ESSGPARGIA IVSVLVILIS IVIFCLETLP EFRDEKDYPA STSQDSFEAA GNSTSGSRAG ASSFSDPFF VVETLCIIWF SFELLVRFFA CPSKATFSRN IMNLIDIVAI IPYFITLGTE LAERQGNGQQ AMSLAILRVI R LVRVFRIF KLSRHSKGLQ ILGQTLKASM RELGLLIFFL FIGVILFSSA VYFAEADDPT SGFSSIPDAF WWAVVTMTTV GY GDMHPVT IGGKIVGSLC AIAGVLTIAL PVPVIVSNFN YFYHRETEG |
-Macromolecule #2: Voltage-gated potassium channel subunit beta-2
Macromolecule | Name: Voltage-gated potassium channel subunit beta-2 / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO EC number: Oxidoreductases; Acting on the CH-OH group of donors; With NAD+ or NADP+ as acceptor |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 36.704254 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: RQLQFYRNLG KSGLRVSCLG LGTWVTFGGQ ITDEMAEQLM TLAYDNGINL FDTAEVYAAG KAEVVLGNII KKKGWRRSSL VITTKIFWG GKAETERGLS RKHIIEGLKA SLERLQLEYV DVVFANRPDP NTPMEETVRA MTHVINQGMA MYWGTSRWSS M EIMEAYSV ...String: RQLQFYRNLG KSGLRVSCLG LGTWVTFGGQ ITDEMAEQLM TLAYDNGINL FDTAEVYAAG KAEVVLGNII KKKGWRRSSL VITTKIFWG GKAETERGLS RKHIIEGLKA SLERLQLEYV DVVFANRPDP NTPMEETVRA MTHVINQGMA MYWGTSRWSS M EIMEAYSV ARQFNLTPPI CEQAEYHMFQ REKVEVQLPE LFHKIGVGAM TWSPLACGIV SGKYDSGIPP YSRASLKGYQ WL KDKILSE EGRRQQAKLK ELQAIAERLG CTLPQLAIAW CLRNEGVSSV LLGASNADQL MENIGAIQVL PKLSSSIIHE IDS ILGNKP YS |
-Macromolecule #3: Potassium voltage-gated channel subfamily A member 3
Macromolecule | Name: Potassium voltage-gated channel subfamily A member 3 / type: protein_or_peptide / ID: 3 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 12.777475 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: QDCCGERVVI NISGLRFETQ LKTLCQFPET LLGDPKRRMR YFDPLRNEYF FDRNRPSFDA ILYYYQSGGR IRRPVNVPID IFSEEIRFY QLGEEAMEKF REDEGFL |
-Macromolecule #4: POTASSIUM ION
Macromolecule | Name: POTASSIUM ION / type: ligand / ID: 4 / Number of copies: 4 / Formula: K |
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Molecular weight | Theoretical: 39.098 Da |
-Macromolecule #5: NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
Macromolecule | Name: NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / type: ligand / ID: 5 / Number of copies: 4 / Formula: NAP |
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Molecular weight | Theoretical: 743.405 Da |
Chemical component information | ChemComp-NAP: |
-Macromolecule #6: water
Macromolecule | Name: water / type: ligand / ID: 6 / Number of copies: 116 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-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 | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 65.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF Details: The above mentioned 3.4 Ang resolution was obtained for TM domain after application of C4 symmetry. The soluble domain map (another map deposited here) was resolved to 2.9 Ang. Number images used: 177130 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |