7E84

CryoEM structure of human Kv4.2-KChIP1 complex


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.10 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural basis of gating modulation of Kv4 channel complexes.

Kise, Y.Kasuya, G.Okamoto, H.H.Yamanouchi, D.Kobayashi, K.Kusakizako, T.Nishizawa, T.Nakajo, K.Nureki, O.

(2021) Nature 599: 158-164

  • DOI: https://doi.org/10.1038/s41586-021-03935-z
  • Primary Citation of Related Structures:  
    7E7Z, 7E83, 7E84, 7E87, 7E89, 7E8B, 7E8E, 7E8G, 7E8H, 7F0J, 7F3F

  • PubMed Abstract: 

    Modulation of voltage-gated potassium (Kv) channels by auxiliary subunits is central to the physiological function of channels in the brain and heart 1,2 . 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 1-5 . 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.


  • Organizational Affiliation

    Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan. yoshiaki.kise@bs.s.u-toyko.ac.jp.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Potassium voltage-gated channel subfamily D member 2A,
B,
C [auth D],
D [auth G]
492Octodon degusMutation(s): 0 
Gene Names: Kcnd2
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for Q9NZV8 (Homo sapiens)
Explore Q9NZV8 
Go to UniProtKB:  Q9NZV8
PHAROS:  Q9NZV8
GTEx:  ENSG00000184408 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9NZV8
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Kv channel-interacting protein 1E,
F [auth H],
G [auth J],
H [auth L]
181Homo sapiensMutation(s): 0 
Gene Names: KCNIP1KCHIP1VABP
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for Q9NZI2 (Homo sapiens)
Explore Q9NZI2 
Go to UniProtKB:  Q9NZI2
PHAROS:  Q9NZI2
GTEx:  ENSG00000182132 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9NZI2
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.10 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Japan Society for the Promotion of Science (JSPS)Japan--

Revision History  (Full details and data files)

  • Version 1.0: 2021-10-13
    Type: Initial release
  • Version 1.1: 2022-02-16
    Changes: Database references
  • Version 1.2: 2024-06-05
    Changes: Data collection