美国洛克菲勒大学Roderick MacKinnon团队的一项最新研究解析了人类KCNQ1调制与门控的结构基础。2019年12月26日，《细胞》杂志在线发表了这项成果。

通过使用冷冻电镜（cryo-EM），研究人员发现出KCNE3将跨过单膜的螺旋束对着KCNQ1的位置，似乎将电压传感器锁定在其去极化构象中。没有PIP2时，孔保持封闭。加载后，PIP2占据了内膜小叶内KCNQ1上的一个位点，这会触发大的构象变化，从而导致孔门扩张。在Kv7通道中，可能会保留PIP2激活的这种机制。

据介绍，KCNQ1，也称为Kv7.1，是电压依赖的K⁺通道，可调节胃酸分泌、盐和葡萄糖的体内稳态以及心律。它的功能特性是通过与β亚基KCNE1-5的共同装配以组织特异性的方式调节的。在不可兴奋的细胞中，KCNQ1与KCNE3形成复合物，从而抑制了在负膜电压下的通道关闭，否则该通道将被关闭。孔开放受信号脂质PIP2调控。

附：英文原文

Title: Structural Basis of Human KCNQ1 Modulation and Gating

Author: Ji Sun, Roderick MacKinnon

Issue&Volume: December 26, 2019

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 leaflet, which triggers a large conformational change that leads to dilation of the pore’s gate. It is likely that this mechanism of PIP2 activation is conserved among Kv7 channels.

DOI: 10.1016/j.cell.2019.12.003

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31329-7