HERG S4-S5 linker acts as a voltage-dependent ligand that binds to the activation gate and locks it in a closed state.

ABSTRACT: Delayed-rectifier potassium channels (hERG and KCNQ1) play a major role in cardiac repolarization. These channels are formed by a tetrameric pore (S5-S6) surrounded by four voltage sensor domains (S1-S4). Coupling between voltage sensor domains and the pore activation gate is critical for channel voltage-dependence. However, molecular mechanisms remain elusive. Herein, we demonstrate that covalently binding, through a disulfide bridge, a peptide mimicking the S4-S5 linker (S4-S5_L) to the channel S6 C-terminus (S6_T) completely inhibits hERG. This shows that channel S4-S5_L is sufficient to stabilize the pore activation gate in its closed state. Conversely, covalently binding a peptide mimicking S6_T to the channel S4-S5_L prevents its inhi

SUBMITTER: Malak OA 

PROVIDER: S-EPMC5427910 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature