TASK2 (also known as KCNK5) channels generate pH-gated leak-type K + currents to control cellular electrical excitability 1 – 3 . TASK2 is involved in the regulation of breathing by chemosensory neurons of the retrotrapezoid nucleus in the brainstem 4 – 6 and pH homeostasis by kidney proximal tubule cells 7 , 8 . These roles depend on channel activation by intracellular and extracellular alkalization 3 , 8 , 9 , but the mechanistic basis for TASK2 gating by pH is unknown. Here we present cryo-electron microscopy structures of Mus musculus TASK2 in lipid nanodiscs in open and closed conformations. We identify two gates, distinct from previously observed K + channel gates, controlled by stimuli on either side of the membrane. Intracellular gating involves lysine protonation on inner helices and the formation of a protein seal between the cytoplasm and the channel. Extracellular gating involves arginine protonation on the channel surface and correlated conformational changes that displace the K + -selectivity filter to render it nonconductive. These results explain how internal and external protons control intracellular and selectivity filter gates to modulate TASK2 activity. The authors report on the structure of the K + channel TASK2 and how this channel opens in response to pH changes on either side of the cell membrane.

中文翻译：

---

双孔结构域 K+ 通道 TASK2 的 pH 门控结构基础

TASK2（也称为 KCNK5）通道产生 pH 门控泄漏型 K + 电流以控制细胞电兴奋性 1 – 3。TASK2 参与调节脑干 4-6 中逆梯形核的化学感觉神经元的呼吸和肾脏近端小管细胞 7、8 的 pH 稳态。这些作用取决于细胞内和细胞外碱化 3、8、9 的通道激活，但 TASK2 通过 pH 进行门控的机制基础尚不清楚。在这里，我们展示了 Mus musculus TASK2 在脂质纳米盘中的开放和封闭构象的低温电子显微镜结构。我们确定了两个门，与先前观察到的 K + 通道门不同，由膜两侧的刺激控制。细胞内门控涉及内部螺旋上的赖氨酸质子化以及在细胞质和通道之间形成蛋白质密封。细胞外门控涉及通道表面上的精氨酸质子化和相关的构象变化，这些变化取代了 K + -选择性过滤器，使其不导电。这些结果解释了内部和外部质子如何控制细胞内和选择性过滤门以调节 TASK2 活性。作者报告了 K + 通道 TASK2 的结构以及该通道如何响应细胞膜两侧的 pH 变化而打开。这些结果解释了内部和外部质子如何控制细胞内和选择性过滤门以调节 TASK2 活性。作者报告了 K + 通道 TASK2 的结构以及该通道如何响应细胞膜两侧的 pH 变化而打开。这些结果解释了内部和外部质子如何控制细胞内和选择性过滤门以调节 TASK2 活性。作者报告了 K + 通道 TASK2 的结构以及该通道如何响应细胞膜两侧的 pH 变化而打开。