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- EMDB-31016: CryoEM structure of human Kv4.2-DPP6S-KChIP1 complex, transmembra... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-31016 | |||||||||
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Title | CryoEM structure of human Kv4.2-DPP6S-KChIP1 complex, transmembrane and intracellular region | |||||||||
![]() | map I | |||||||||
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![]() | membrane protein | |||||||||
Function / homology | ![]() Kv4.3-KChIP1 channel complex / 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 / potassium ion export across plasma membrane / membrane repolarization / Voltage gated Potassium channels / regulation of potassium ion transmembrane transport / postsynaptic specialization membrane ...Kv4.3-KChIP1 channel complex / 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 / potassium ion export across plasma membrane / membrane repolarization / Voltage gated Potassium channels / regulation of potassium ion transmembrane transport / postsynaptic specialization membrane / anchoring junction / neuronal cell body membrane / regulation of heart contraction / locomotor rhythm / plasma membrane raft / action potential / voltage-gated potassium channel activity / potassium channel activity / potassium channel regulator activity / neuronal action potential / voltage-gated potassium channel complex / muscle contraction / sensory perception of pain / potassium ion transmembrane transport / serine-type peptidase activity / GABA-ergic synapse / protein localization to plasma membrane / protein homooligomerization / cytoplasmic side of plasma membrane / perikaryon / chemical synaptic transmission / cellular response to hypoxia / postsynaptic membrane / transmembrane transporter binding / dendritic spine / neuronal cell body / dendrite / synapse / calcium ion binding / glutamatergic synapse / proteolysis / membrane / metal ion binding / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
![]() | Kise Y / Nureki O | |||||||||
Funding support | ![]()
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![]() | ![]() 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 | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 12.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18 KB 18 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.7 KB | Display | ![]() |
Images | ![]() | 64.7 KB | ||
Masks | ![]() | 101 MB | ![]() | |
Filedesc metadata | ![]() | 5.6 KB | ||
Others | ![]() ![]() | 77.5 MB 77.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 740.4 KB | Display | ![]() |
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Full document | ![]() | 740 KB | Display | |
Data in XML | ![]() | 17.4 KB | Display | |
Data in CIF | ![]() | 22.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7e8eMC ![]() 7e7zC ![]() 7e83C ![]() 7e84C ![]() 7e87C ![]() 7e89C ![]() 7e8bC ![]() 7e8gC ![]() 7e8hC ![]() 7f0jC ![]() 7f3fC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | map I | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.00268 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
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-Half map: #1
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Density Histograms |
-Half map: #2
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Density Histograms |
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Sample components
-Entire : human Kv4.2-DPP6S-KChIP1 complex
Entire | Name: human Kv4.2-DPP6S-KChIP1 complex |
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Components |
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-Supramolecule #1: human Kv4.2-DPP6S-KChIP1 complex
Supramolecule | Name: human Kv4.2-DPP6S-KChIP1 complex / type: cell / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Kv channel-interacting protein 1
Macromolecule | Name: Kv channel-interacting protein 1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 21.242941 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: PEGLEQLEAQ TNFTKRELQV LYRGFKNECP SGVVNEDTFK QIYAQFFPHG DASTYAHYLF NAFDTTQTGS VKFEDFVTAL SILLRGTVH EKLRWTFNLY DINKDGYINK EEMMDIVKAI YDMMGKYTYP VLKEDTPRQH VDVFFQKMDK NKDGIVTLDE F LESCQEDD NIMRSLQLFQ NVM UniProtKB: A-type potassium channel modulatory protein KCNIP1 |
-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: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 55.755738 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: AAGVAAWLPF ARAAAIGWMP VASGPMPAPP RQERKRTQDA LIVLNVSGTR FQTWQDTLER YPDTLLGSSE RDFFYHPETQ QYFFDRDPD IFRHILNFYR TGKLHYPRHE CISAYDEELA FFGLIPEIIG DCCYEEYKDR RRENAERLQD DADTDTAGES A LPTMTARQ ...String: AAGVAAWLPF ARAAAIGWMP VASGPMPAPP RQERKRTQDA LIVLNVSGTR FQTWQDTLER YPDTLLGSSE RDFFYHPETQ QYFFDRDPD IFRHILNFYR TGKLHYPRHE CISAYDEELA FFGLIPEIIG DCCYEEYKDR RRENAERLQD DADTDTAGES A LPTMTARQ RVWRAFENPH TSTMALVFYY VTGFFIAVSV IANVVETVPC GSSPGHIKEL PCGERYAVAF FCLDTACVMI FT VEYLLRL AAAPSRYRFV RSVMSIIDVV AILPYYIGLV MTDNEDVSGA FVTLRVFRVF RIFKFSRHSQ GLRILGYTLK SCA SELGFL LFSLTMAIII FATVMFYAEK GSSASKFTSI PAAFWYTIVT MTTLGYGDMV PKTIAGKIFG SICSLSGVLV IALP VPVIV SNFSRIYHQN QRADKRRAQK KARLARIRAA KSGSANAYMQ SKRSGLLSNQ LQSSEDEQAF VSKSGSSFET QHHHL LHCL EKTTNHEFVD UniProtKB: A-type voltage-gated potassium channel KCND2 |
-Macromolecule #3: Dipeptidyl aminopeptidase-like protein 6
Macromolecule | Name: Dipeptidyl aminopeptidase-like protein 6 / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 3.032829 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: AAAAKGIAIA LLVILVICSL IVTSVILLTP A UniProtKB: A-type potassium channel modulatory protein DPP6 |
-Macromolecule #4: Kv channel-interacting protein 1
Macromolecule | Name: Kv channel-interacting protein 1 / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 21.145826 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: EGLEQLEAQT NFTKRELQVL YRGFKNECPS GVVNEDTFKQ IYAQFFPHGD ASTYAHYLFN AFDTTQTGSV KFEDFVTALS ILLRGTVHE KLRWTFNLYD INKDGYINKE EMMDIVKAIY DMMGKYTYPV LKEDTPRQHV DVFFQKMDKN KDGIVTLDEF L ESCQEDDN IMRSLQLFQN VM UniProtKB: A-type potassium channel modulatory protein KCNIP1 |
-Macromolecule #5: Dipeptidyl aminopeptidase-like protein 6
Macromolecule | Name: Dipeptidyl aminopeptidase-like protein 6 / type: protein_or_peptide / ID: 5 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 2.819595 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: AKGIAIALLV ILVICSLIVT SVILLTPA UniProtKB: A-type potassium channel modulatory protein DPP6 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |