Phosphatidylinositol 4,5-bisphosphate activation mechanism of human KCNQ5.

ABSTRACT: The human voltage-gated potassium channels KCNQ2, KCNQ3, and KCNQ5 can form homo- and heterotetrameric channels that are responsible for generating the neuronal M current and maintaining the membrane potential stable. Activation of KCNQ channels requires both the depolarization of membrane potential and phosphatidylinositol 4,5-bisphosphate (PIP₂). Here, we report cryoelectron microscopy structures of the human KCNQ5-calmodulin (CaM) complex in the apo, PIP₂-bound, and both PIP₂- and the activator HN37-bound states in either a closed or an open conformation. In the closed conformation, a PIP₂ molecule binds in the middle of the groove between two adjacent voltage-sensing domains (VSDs), whereas in the open conformation, one additional PIP_2</

SUBMITTER: Yang Z 

PROVIDER: S-EPMC12002238 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature