A generic binding pocket for small molecule I_Ks activators at the extracellular inter-subunit interface of KCNQ1 and KCNE1 channel complexes.

ABSTRACT: The cardiac I_Ks ion channel comprises KCNQ1, calmodulin, and KCNE1 in a dodecameric complex which provides a repolarizing current reserve at higher heart rates and protects from arrhythmia syndromes that cause fainting and sudden death. Pharmacological activators of I_Ks are therefore of interest both scientifically and therapeutically for treatment of I_Ks loss-of-function disorders. One group of chemical activators are only active in the presence of the accessory KCNE1 subunit and here we investigate this phenomenon using molecular modeling techniques and mutagenesis scanning in mammalian cells. A generalized activator binding pocket is formed extracellularly by KCNE1, the domain-swapped S1 helices of one KCNQ1 subunit and

SUBMITTER: Chan M 

PROVIDER: S-EPMC10501768 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature