RGD Reference Report - Activation and closed-state inactivation mechanisms of the human voltage-gated KV4 channel complexes. - Rat Genome Database

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Activation and closed-state inactivation mechanisms of the human voltage-gated KV4 channel complexes.

Authors: Ye, Wenlei  Zhao, Hongtu  Dai, Yaxin  Wang, Yingdi  Lo, Yu-Hua  Jan, Lily Yeh  Lee, Chia-Hsueh 
Citation: Ye W, etal., Mol Cell. 2022 Jul 7;82(13):2427-2442.e4. doi: 10.1016/j.molcel.2022.04.032. Epub 2022 May 20.
RGD ID: 405866206
Pubmed: PMID:35597238   (View Abstract at PubMed)
PMCID: PMC9271590   (View Article at PubMed Central)
DOI: DOI:10.1016/j.molcel.2022.04.032   (Journal Full-text)

The voltage-gated ion channel activity depends on both activation (transition from the resting state to the open state) and inactivation. Inactivation is a self-restraint mechanism to limit ion conduction and is as crucial to membrane excitability as activation. Inactivation can occur when the channel is open or closed. Although open-state inactivation is well understood, the molecular basis of closed-state inactivation has remained elusive. We report cryo-EM structures of human KV4.2 channel complexes in inactivated, open, and closed states. Closed-state inactivation of KV4 involves an unprecedented symmetry breakdown for pore closure by only two of the four S4-S5 linkers, distinct from known mechanisms of open-state inactivation. We further capture KV4 in a putative resting state, revealing how voltage sensor movements control the pore. Moreover, our structures provide insights regarding channel modulation by KChIP2 and DPP6 auxiliary subunits. Our findings elucidate mechanisms of closed-state inactivation and voltage-dependent activation of the KV4 channel.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Kcnd2Ratpotassium ion transmembrane transport involved_inIDA PMID:35597238UniProt 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Kcnd2Ratplasma membrane located_inIDA PMID:35597238UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Kcnd2RatA-type (transient outward) potassium channel activity enablesIDA PMID:35597238UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Kcnd2  (potassium voltage-gated channel subfamily D member 2)


Additional Information