RGD Reference Report - Regulation of Eag1 gating by its intracellular domains. - Rat Genome Database

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Regulation of Eag1 gating by its intracellular domains.

Authors: Whicher, Jonathan R  MacKinnon, Roderick 
Citation: Whicher JR and MacKinnon R, Elife. 2019 Sep 6;8:e49188. doi: 10.7554/eLife.49188.
RGD ID: 405866186
Pubmed: PMID:31490124   (View Abstract at PubMed)
PMCID: PMC6731095   (View Article at PubMed Central)
DOI: DOI:10.7554/eLife.49188   (Journal Full-text)

Voltage-gated potassium channels (Kvs) are gated by transmembrane voltage sensors (VS) that move in response to changes in membrane voltage. Kv10.1 or Eag1 also has three intracellular domains: PAS, C-linker, and CNBHD. We demonstrate that the Eag1 intracellular domains are not required for voltage-dependent gating but likely interact with the VS to modulate gating. We identified specific interactions between the PAS, CNBHD, and VS that modulate voltage-dependent gating and provide evidence that VS movement destabilizes these interactions to promote channel opening. Additionally, mutation of these interactions renders Eag1 insensitive to calmodulin inhibition. The structure of the calmodulin insensitive mutant in a pre-open conformation suggests that channel opening may occur through a rotation of the intracellular domains and calmodulin may prevent this rotation by stabilizing interactions between the VS and intracellular domains. Intracellular domains likely play a similar modulatory role in voltage-dependent gating of the related Kv11-12 channels.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Kcnh1Ratpotassium ion transport involved_inIDA PMID:31490124UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Kcnh1Ratdelayed rectifier potassium channel activity enablesIDA PMID:31490124UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Kcnh1  (potassium voltage-gated channel subfamily H member 1)


Additional Information