+ Open data
Open data
- Basic information
Basic information
| Entry | Database: EMDB / ID: EMD-31013 | |||||||||
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| Title | CryoEM structure of human Kv4.2-DPP6S complex | |||||||||
|  Map data | map E | |||||||||
|  Sample | 
 | |||||||||
|  Keywords | membrane protein | |||||||||
| Function / homology |  Function and homology information Kv4.2-KChIP2 channel complex / A-type (transient outward) potassium channel activity / Phase 1 - inactivation of fast Na+ channels / voltage-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / membrane repolarization / Voltage gated Potassium channels / regulation of potassium ion transmembrane transport / anchoring junction / postsynaptic specialization membrane / neuronal cell body membrane ...Kv4.2-KChIP2 channel complex / A-type (transient outward) potassium channel activity / Phase 1 - inactivation of fast Na+ channels / voltage-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / membrane repolarization / Voltage gated Potassium channels / regulation of potassium ion transmembrane transport / anchoring junction / postsynaptic specialization membrane / neuronal cell body membrane / regulation of heart contraction / locomotor rhythm / action potential / plasma membrane raft / voltage-gated potassium channel activity / potassium channel regulator activity / neuronal action potential / voltage-gated potassium channel complex / potassium ion transmembrane transport / sensory perception of pain / serine-type peptidase activity / muscle contraction / protein localization to plasma membrane / protein homooligomerization / GABA-ergic synapse / perikaryon / cellular response to hypoxia / chemical synaptic transmission / dendritic spine / postsynaptic membrane / neuronal cell body / glutamatergic synapse / proteolysis / metal ion binding / membrane / plasma membrane Similarity search - Function | |||||||||
| Biological species |  Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 4.2 Å | |||||||||
|  Authors | Kise Y / Nureki O | |||||||||
| Funding support |  Japan, 1 items 
 | |||||||||
|  Citation |  Journal: Nature / Year: 2021 Title: Structural basis of gating modulation of Kv4 channel complexes. Authors: Yoshiaki Kise / Go Kasuya / Hiroyuki H Okamoto / Daichi Yamanouchi / Kan Kobayashi / Tsukasa Kusakizako / Tomohiro Nishizawa / Koichi Nakajo / Osamu Nureki /  Abstract: Modulation of voltage-gated potassium (Kv) channels by auxiliary subunits is central to the physiological function of channels in the brain and heart. Native Kv4 tetrameric channels form ...Modulation of voltage-gated potassium (Kv) channels by auxiliary subunits is central to the physiological function of channels in the brain and heart. Native Kv4 tetrameric channels form macromolecular ternary complexes with two auxiliary β-subunits-intracellular Kv channel-interacting proteins (KChIPs) and transmembrane dipeptidyl peptidase-related proteins (DPPs)-to evoke rapidly activating and inactivating A-type currents, which prevent the backpropagation of action potentials. However, the modulatory mechanisms of Kv4 channel complexes remain largely unknown. Here we report cryo-electron microscopy structures of the Kv4.2-DPP6S-KChIP1 dodecamer complex, the Kv4.2-KChIP1 and Kv4.2-DPP6S octamer complexes, and Kv4.2 alone. The structure of the Kv4.2-KChIP1 complex reveals that the intracellular N terminus of Kv4.2 interacts with its C terminus that extends from the S6 gating helix of the neighbouring Kv4.2 subunit. KChIP1 captures both the N and the C terminus of Kv4.2. In consequence, KChIP1 would prevent N-type inactivation and stabilize the S6 conformation to modulate gating of the S6 helices within the tetramer. By contrast, unlike the reported auxiliary subunits of voltage-gated channel complexes, DPP6S interacts with the S1 and S2 helices of the Kv4.2 voltage-sensing domain, which suggests that DPP6S stabilizes the conformation of the S1-S2 helices. DPP6S may therefore accelerate the voltage-dependent movement of the S4 helices. KChIP1 and DPP6S do not directly interact with each other in the Kv4.2-KChIP1-DPP6S ternary complex. Thus, our data suggest that two distinct modes of modulation contribute in an additive manner to evoke A-type currents from the native Kv4 macromolecular complex. | |||||||||
| History | 
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- Structure visualization
Structure visualization
| Movie | 
 
 
  Movie viewer | 
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| Structure viewer | EM map:  SurfView  Molmil  Jmol/JSmol | 
| Supplemental images | 
- Downloads & links
Downloads & links
-EMDB archive
| Map data |  emd_31013.map.gz | 20 MB |  EMDB map data format | |
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| Header (meta data) |  emd-31013-v30.xml  emd-31013.xml | 20.1 KB 20.1 KB | Display Display |  EMDB header | 
| FSC (resolution estimation) |  emd_31013_fsc.xml | 11.8 KB | Display |  FSC data file | 
| Images |  emd_31013.png | 74 KB | ||
| Masks |  emd_31013_msk_1.map | 139.6 MB |  Mask map | |
| Filedesc metadata |  emd-31013.cif.gz | 6.5 KB | ||
| Others |  emd_31013_half_map_1.map.gz  emd_31013_half_map_2.map.gz | 108.1 MB 108.1 MB | ||
| Archive directory |  http://ftp.pdbj.org/pub/emdb/structures/EMD-31013  ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31013 | HTTPS FTP | 
-Validation report
| Summary document |  emd_31013_validation.pdf.gz | 771.2 KB | Display |  EMDB validaton report | 
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| Full document |  emd_31013_full_validation.pdf.gz | 770.8 KB | Display | |
| Data in XML |  emd_31013_validation.xml.gz | 18 KB | Display | |
| Data in CIF |  emd_31013_validation.cif.gz | 23.8 KB | Display | |
| Arichive directory |  https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31013  ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31013 | HTTPS FTP | 
-Related structure data
| Related structure data |  7e8bMC  7e7zC  7e83C  7e84C  7e87C  7e89C  7e8eC  7e8gC  7e8hC  7f0jC  7f3fC M: atomic model generated by this map C: citing same article ( | 
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| Similar structure data | 
- Links
Links
| EMDB pages |  EMDB (EBI/PDBe) /  EMDataResource | 
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| Related items in Molecule of the Month | 
- Map
Map
| File |  Download / File: emd_31013.map.gz / Format: CCP4 / Size: 139.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Annotation | map E | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
 
 Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Density | 
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Details | EMDB XML: 
 CCP4 map header: 
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-Supplemental data
-Mask #1
| File |  emd_31013_msk_1.map | ||||||||||||
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| Projections & Slices | 
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| Density Histograms | 
-Half map: #1
| File | emd_31013_half_map_1.map | ||||||||||||
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| Projections & Slices | 
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| Density Histograms | 
-Half map: #2
| File | emd_31013_half_map_2.map | ||||||||||||
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| Projections & Slices | 
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| Density Histograms | 
- Sample components
Sample components
-Entire : human Kv4.2-DPP6S complex
| Entire | Name: human Kv4.2-DPP6S complex | 
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| Components | 
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-Supramolecule #1: human Kv4.2-DPP6S complex
| Supramolecule | Name: human Kv4.2-DPP6S complex / type: cell / ID: 1 / Parent: 0 / Macromolecule list: all | 
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| Source (natural) | Organism:  Homo sapiens (human) | 
-Macromolecule #1: Dipeptidyl aminopeptidase-like protein 6
| Macromolecule | Name: Dipeptidyl aminopeptidase-like protein 6 / 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: 86.392797 KDa | 
| Recombinant expression | Organism:  Homo sapiens (human) | 
| Sequence | String: WKGIAIALLV ILVICSLIVT SVILLTPAED NSLSQKKKVT VEDLFSEDFK IHDPEAKWIS DTEFIYREQK GTVRLWNVET  NTSTVLIEG KKIESLRAIR YEISPDREYA LFSYNVEPIY QHSYTGYYVL SKIPHGDPQS LDPPEVSNAK LQYAGWGPKG Q QLIFIFEN  ...String: WKGIAIALLV ILVICSLIVT SVILLTPAED NSLSQKKKVT VEDLFSEDFK IHDPEAKWIS DTEFIYREQK GTVRLWNVET  NTSTVLIEG KKIESLRAIR YEISPDREYA LFSYNVEPIY QHSYTGYYVL SKIPHGDPQS LDPPEVSNAK LQYAGWGPKG Q QLIFIFEN NIYYCAHVGK QAIRVVSTGK EGVIYNGLSD WLYEEEILKT HIAHWWSPDG TRLAYAAIND SRVPIMELPT YT GSIYPTV KPYHYPKAGS ENPSISLHVI GLNGPTHDLE MMPPDDPRMR EYYITMVKWA TSTKVAVTWL NRAQNVSILT LCD ATTGVC TKKHEDESEA WLHRQNEEPV FSKDGRKFFF IRAIPQGGRG KFYHITVSSS QPNSSNDNIQ SITSGDWDVT KILA YDEKG NKIYFLSTED LPRRRQLYSA NTVGNFNRQC LSCDLVENCT YFSASFSHSM DFFLLKCEGP GVPMVTVHNT TDKKK MFDL ETNEHVKKAI NDRQMPKVEY RDIEIDDYNL PMQILKPATF TDTTHYPLLL VVDGTPGSQS VAEKFEVSWE TVMVSS HGA VVVKCDGRGS GFQGTKLLHE VRRRLGLLEE KDQMEAVRTM LKEQYIDRTR VAVFGKDYGG YLSTYILPAK GENQGQT FT CGSALSPITD FKLYASAFSE RYLGLHGLDN RAYEMTKVAH RVSALEEQQF LIIHPTADEK IHFQHTAELI TQLIRGKA N YSLQIYPDES HYFTSSSLKQ HLYRSIINFF VECFRI UniProtKB: A-type potassium channel modulatory protein DPP6 | 
-Macromolecule #2: Potassium voltage-gated channel subfamily D member 2
| Macromolecule | Name: Potassium voltage-gated channel subfamily D member 2 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO | 
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| Source (natural) | Organism:  Homo sapiens (human) | 
| Molecular weight | Theoretical: 45.297133 KDa | 
| Recombinant expression | Organism:  Homo sapiens (human) | 
| Sequence | String: DALIVLNVSG TRFQTWQDTL ERYPDTLLGS SERDFFYHPE TQQYFFDRDP DIFRHILNFY RTGKLHYPRH ECISAYDEEL  AFFGLIPEI IGDCCYEEYK DRRRENAERL QDDADTDTAG ESALPTMTAR QRVWRAFENP HTSTMALVFY YVTGFFIAVS V IANVVETV  ...String: DALIVLNVSG TRFQTWQDTL ERYPDTLLGS SERDFFYHPE TQQYFFDRDP DIFRHILNFY RTGKLHYPRH ECISAYDEEL  AFFGLIPEI IGDCCYEEYK DRRRENAERL QDDADTDTAG ESALPTMTAR QRVWRAFENP HTSTMALVFY YVTGFFIAVS V IANVVETV PCGSSPGHIK ELPCGERYAV AFFCLDTACV MIFTVEYLLR LAAAPSRYRF VRSVMSIIDV VAILPYYIGL VM TDNEDVS GAFVTLRVFR VFRIFKFSRH SQGLRILGYT LKSCASELGF LLFSLTMAII IFATVMFYAE KGSSASKFTS IPA AFWYTI VTMTTLGYGD MVPKTIAGKI FGSICSLSGV LVIALPVPVI VSNFSRIYHQ NQRADKRRAQ KKARLARIRA AK UniProtKB: A-type voltage-gated potassium channel KCND2 | 
-Macromolecule #3: Potassium voltage-gated channel subfamily D member 2
| Macromolecule | Name: Potassium voltage-gated channel subfamily D member 2 / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO | 
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| Source (natural) | Organism:  Homo sapiens (human) | 
| Molecular weight | Theoretical: 45.167953 KDa | 
| Recombinant expression | Organism:  Homo sapiens (human) | 
| Sequence | String: DALIVLNVSG TRFQTWQDTL ERYPDTLLGS SERDFFYHPE TQQYFFDRDP DIFRHILNFY RTGKLHYPRH ECISAYDEEL  AFFGLIPEI IGDCCYEEYK DRRRENAERL QDDADTDTAG ESALPTMTAR QRVWRAFENP HTSTMALVFY YVTGFFIAVS V IANVVETV  ...String: DALIVLNVSG TRFQTWQDTL ERYPDTLLGS SERDFFYHPE TQQYFFDRDP DIFRHILNFY RTGKLHYPRH ECISAYDEEL  AFFGLIPEI IGDCCYEEYK DRRRENAERL QDDADTDTAG ESALPTMTAR QRVWRAFENP HTSTMALVFY YVTGFFIAVS V IANVVETV PCGSSPGHIK ELPCGERYAV AFFCLDTACV MIFTVEYLLR LAAAPSRYRF VRSVMSIIDV VAILPYYIGL VM TDNEDVS GAFVTLRVFR VFRIFKFSRH SQGLRILGYT LKSCASELGF LLFSLTMAII IFATVMFYAE KGSSASKFTS IPA AFWYTI VTMTTLGYGD MVPKTIAGKI FGSICSLSGV LVIALPVPVI VSNFSRIYHQ NQRADKRRAQ KKARLARIRA A UniProtKB: A-type voltage-gated potassium channel KCND2 | 
-Experimental details
-Structure determination
| Method | cryo EM | 
|---|---|
|  Processing | single particle reconstruction | 
| Aggregation state | particle | 
- Sample preparation
Sample preparation
| Buffer | pH: 8 | 
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| Vitrification | Cryogen name: ETHANE | 
- Electron microscopy
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: 48.0 e/Å2 | 
| Electron beam | Acceleration voltage: 300 kV / Electron source:  FIELD EMISSION GUN | 
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD | 
| Experimental equipment |  Model: Titan Krios / Image courtesy: FEI Company | 
+ Image processing
Image processing
-Atomic model buiding 1
| Refinement | Space: REAL | 
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| Output model |  PDB-7e8b:  | 
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