+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31399 | |||||||||
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Title | CryoEM structure of human Kv4.2 | |||||||||
Map data | ||||||||||
Sample |
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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 / postsynaptic specialization membrane / anchoring junction / regulation of heart contraction / action potential ...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 / postsynaptic specialization membrane / anchoring junction / regulation of heart contraction / action potential / neuronal cell body membrane / locomotor rhythm / voltage-gated potassium channel activity / plasma membrane raft / neuronal action potential / GABA-ergic synapse / voltage-gated potassium channel complex / potassium ion transmembrane transport / sensory perception of pain / muscle contraction / protein homooligomerization / cellular response to hypoxia / perikaryon / chemical synaptic transmission / postsynaptic membrane / dendritic spine / neuronal cell body / glutamatergic synapse / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
Authors | Kise Y / Nureki O | |||||||||
Funding support | Japan, 1 items
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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
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_31399.map.gz | 3.8 MB | EMDB map data format | |
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Header (meta data) | emd-31399-v30.xml emd-31399.xml | 14.3 KB 14.3 KB | Display Display | EMDB header |
Images | emd_31399.png | 61.5 KB | ||
Masks | emd_31399_msk_1.map | 30.5 MB | Mask map | |
Others | emd_31399_half_map_1.map.gz emd_31399_half_map_2.map.gz | 20.4 MB 20.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31399 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31399 | HTTPS FTP |
-Related structure data
Related structure data | 7f0jMC 7e7zC 7e83C 7e84C 7e87C 7e89C 7e8bC 7e8eC 7e8gC 7e8hC 7f3fC 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_31399.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.411 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_31399_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_31399_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #1
File | emd_31399_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : human Kv4.2
Entire | Name: human Kv4.2 |
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Components |
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-Supramolecule #1: human Kv4.2
Supramolecule | Name: human Kv4.2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: Potassium voltage-gated channel subfamily D member 2
Macromolecule | Name: Potassium voltage-gated channel subfamily D member 2 / 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: 70.61843 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MAAGVAAWLP FARAAAIGWM PVASGPMPAP PRQERKRTQD ALIVLNVSGT RFQTWQDTLE RYPDTLLGSS ERDFFYHPET QQYFFDRDP DIFRHILNFY RTGKLHYPRH ECISAYDEEL AFFGLIPEII GDCCYEEYKD RRRENAERLQ DDADTDTAGE S ALPTMTAR ...String: MAAGVAAWLP FARAAAIGWM PVASGPMPAP PRQERKRTQD ALIVLNVSGT RFQTWQDTLE RYPDTLLGSS ERDFFYHPET QQYFFDRDP DIFRHILNFY RTGKLHYPRH ECISAYDEEL AFFGLIPEII GDCCYEEYKD RRRENAERLQ DDADTDTAGE S ALPTMTAR QRVWRAFENP HTSTMALVFY YVTGFFIAVS VIANVVETVP CGSSPGHIKE LPCGERYAVA FFCLDTACVM IF TVEYLLR LAAAPSRYRF VRSVMSIIDV VAILPYYIGL VMTDNEDVSG AFVTLRVFRV FRIFKFSRHS QGLRILGYTL KSC ASELGF LLFSLTMAII IFATVMFYAE KGSSASKFTS IPAAFWYTIV TMTTLGYGDM VPKTIAGKIF GSICSLSGVL VIAL PVPVI VSNFSRIYHQ NQRADKRRAQ KKARLARIRA AKSGSANAYM QSKRNGLLSN QLQSSEDEQA FVSKSGSSFE TQHHH LLHC LEKTTNHEFV DEQVFEESCM EVATVNRPSS HSPSLSSQQG VTSTCCSRRH KKTFRIPNAN VSGSHQGSIQ ELSTIQ IRC VERTPLSNSR SSLNAKMEEC VKLNCEQPYV TTAIISIPTP PVTTPEGDDR PESPEYSGGN IVRVSAL |
-Macromolecule #2: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 2 / Number of copies: 4 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
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Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Applied symmetry - Point group: C4 (4 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 70625 |
-Atomic model buiding 1
Refinement | Space: REAL |
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Output model | PDB-7f0j: |