Regulation of Eag1 gating by its intracellular domains.

ABSTRACT: Voltage-gated potassium channels (K_vs) are gated by transmembrane voltage sensors (VS) that move in response to changes in membrane voltage. K_v10.1 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 m

SUBMITTER: Whicher JR 

PROVIDER: S-EPMC6731095 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature