Calmodulin acts as a state-dependent switch to control a cardiac potassium channel opening.

ABSTRACT: Calmodulin (CaM) and phosphatidylinositol 4,5-bisphosphate (PIP₂) are potent regulators of the voltage-gated potassium channel KCNQ1 (K_V7.1), which conducts the cardiac I _Ks current. Although cryo-electron microscopy structures revealed intricate interactions between the KCNQ1 voltage-sensing domain (VSD), CaM, and PIP₂, the functional consequences of these interactions remain unknown. Here, we show that CaM-VSD interactions act as a state-dependent switch to control KCNQ1 pore opening. Combined electrophysiology and molecular dynamics network analysis suggest that VSD transition into the fully activated state allows PIP₂ to compete with CaM for binding to VSD. This leads to conformational changes that alter VSD-pore coupling to

SUBMITTER: Kang PW 

PROVIDER: S-EPMC7732179 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature