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Yorodumi- PDB-7e87: CryoEM structure of the human Kv4.2-DPP6S complex, transmembrane ... -
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-Basic information
Entry | Database: PDB / ID: 7.0E+87 | ||||||
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Title | CryoEM structure of the human Kv4.2-DPP6S complex, transmembrane and intracellular region | ||||||
Components |
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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 / regulation of heart contraction ...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 / regulation of heart contraction / action potential / neuronal cell body membrane / plasma membrane raft / locomotor rhythm / voltage-gated potassium channel activity / neuronal action potential / potassium channel regulator activity / voltage-gated potassium channel complex / GABA-ergic synapse / muscle contraction / potassium ion transmembrane transport / sensory perception of pain / serine-type peptidase activity / protein localization to plasma membrane / protein homooligomerization / cellular response to hypoxia / chemical synaptic transmission / perikaryon / postsynaptic membrane / dendritic spine / neuronal cell body / glutamatergic synapse / proteolysis / membrane / metal ion binding / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | ||||||
Authors | Kise, Y. / Nureki, O. | ||||||
Funding support | Japan, 1items
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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
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7e87.cif.gz | 291.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7e87.ent.gz | 239.4 KB | Display | PDB format |
PDBx/mmJSON format | 7e87.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7e87_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 7e87_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 7e87_validation.xml.gz | 61.2 KB | Display | |
Data in CIF | 7e87_validation.cif.gz | 91 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/e8/7e87 ftp://data.pdbj.org/pub/pdb/validation_reports/e8/7e87 | HTTPS FTP |
-Related structure data
Related structure data | 31011MC 7e7zC 7e83C 7e84C 7e89C 7e8bC 7e8eC 7e8gC 7e8hC 7f0jC 7f3fC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 45297.133 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KCND2, KIAA1044 / Production host: Homo sapiens (human) / References: UniProt: Q9NZV8 #2: Protein | Mass: 45167.953 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KCND2, KIAA1044 / Production host: Homo sapiens (human) / References: UniProt: Q9NZV8 #3: Protein/peptide | Mass: 2934.728 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DPP6 / Production host: Homo sapiens (human) / References: UniProt: P42658 |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: human Kv4.2-DPP6S complex / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 48 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.19_4092: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 91974 / Symmetry type: POINT | ||||||||||||||||||||||||
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