1] Division of Biophysics and Neurobiology, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan [2] Department of Physiological Sciences, Hayama, Kanagawa 240-0193, Japan.
Nat Commun. 2014 Jun 12;5:4100. doi: 10.1038/ncomms5100.
In voltage-gated K(+) channels, membrane depolarization induces an upward movement of the voltage-sensing domains (VSD) that triggers pore opening. KCNQ1 is a voltage-gated K(+) channel and its gating behaviour is substantially modulated by auxiliary subunit KCNE proteins. KCNE1, for example, markedly shifts the voltage dependence of KCNQ1 towards the positive direction and slows down the activation kinetics. Here we identify two phenylalanine residues on KCNQ1, Phe232 on S4 (VSD) and Phe279 on S5 (pore domain) to be responsible for the gating modulation by KCNE1. Phe232 collides with Phe279 during the course of the VSD movement and hinders KCNQ1 channel from opening in the presence of KCNE1. This steric hindrance caused by the bulky amino-acid residues destabilizes the open state and thus shifts the voltage dependence of KCNQ1/KCNE1 channel.
在电压门控钾 (K+) 通道中，膜去极化会引起电压感应结构域 (VSD) 的向上移动，从而触发孔道的开启。KCNQ1 是一种电压门控 K(+) 通道，其门控行为受到辅助亚基 KCNE 蛋白的显著调节。例如，KCNE1 会显著地将 KCNQ1 的电压依赖性向正方向移动，并减缓激活动力学。在这里，我们确定 KCNQ1 上的两个苯丙氨酸残基，S4(VSD)上的 Phe232 和 S5(孔域)上的 Phe279，是由 KCNE1 引起门控调节的原因。在 VSD 运动过程中，Phe232 与 Phe279 发生碰撞，在存在 KCNE1 的情况下阻碍 KCNQ1 通道的开启。这种由大体积氨基酸残基引起的空间位阻使开放状态不稳定，从而改变了 KCNQ1/KCNE1 通道的电压依赖性。
