Secondary structure transitions and dual PIP2 binding define cardiac KCNQ1-KCNE1 channel gating.

ABSTRACT: The KCNQ1 + KCNE1 potassium channel complex produces the slow delayed rectifier current (I_Ks) critical for cardiac repolarization. Loss-of-function mutations in KCNQ1 and KCNE1 cause long QT syndrome (LQTS) types 1 and 5 (LQT1/LQT5), accounting for over one-third of clinical LQTS cases. Despite prior structural work on KCNQ1 and KCNQ1 + KCNE3, the structural basis of KCNQ1 + KCNE1 remains unresolved. Using cryo-electron microscopy and electrophysiology, we determined high-resolution (2.5-3.4 Å) structures of human KCNQ1_APO, and KCNQ1 + KCNE1 in both closed and open states. KCNE1 occupies a pivotal position at the interface of three KCNQ1 subunits, inducing six helix-to-loop transitions in KCNQ1 transmembrane segments. Three of them occur at both ends of the S4-S5 link

SUBMITTER: Zhong L 

PROVIDER: S-EPMC12589563 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature