Structural Basis of Human KCNQ1 Modulation and Gating.

ABSTRACT: KCNQ1, also known as Kv7.1, is a voltage-dependent K⁺ channel that regulates gastric acid secretion, salt and glucose homeostasis, and heart rhythm. Its functional properties are regulated in a tissue-specific manner through co-assembly with beta subunits KCNE1-5. In non-excitable cells, KCNQ1 forms a complex with KCNE3, which suppresses channel closure at negative membrane voltages that otherwise would close it. Pore opening is regulated by the signaling lipid PIP2. Using cryoelectron microscopy (cryo-EM), we show that KCNE3 tucks its single-membrane-spanning helix against KCNQ1, at a location that appears to lock the voltage sensor in its depolarized conformation. Without PIP2, the pore remains closed. Upon addition, PIP2 occupies a site on KCNQ1 within the inner membrane leaf

SUBMITTER: Sun J 

PROVIDER: S-EPMC7083075 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature