小柯机器人

K+通道TASK2双孔结构域pH门控的结构基础获解析
2020-10-02 23:33

美国加州大学伯克利分校Stephen G. Brohawn研究团队的最新研究解析了K+通道TASK2双孔结构域pH门控的结构基础。该研究于2020年9月30日在线发表于国际学术期刊《自然》。

研究人员解析了脂质纳米圆盘中小鼠TASK2开放和封闭构象的冷冻电镜结构。研究人员确定了受膜两侧刺激调控的两个门,这与以前观察到的K+通道门不同。细胞内侧门通过内螺旋上的赖氨酸质子化在细胞质和通道之间形成蛋白质密封。细胞外侧门利用通道表面的精氨酸质子化和相关的构象变化使得K+选择性过滤发生位移,导致其不导电。这些结果解释了内部和外部质子如何调控细胞内选择性滤过门以调节TASK2的活性。

据介绍,TASK2(也称为KCNK5)通道产生pH门控的泄漏型K+电流,以控制细胞的兴奋性。TASK2通过脑干内梯形核的化学感觉神经元调节呼吸以及通过肾脏近端肾小管细胞调控pH稳态。这些作用取决于细胞内和细胞外碱化通道的激活作用,但是通过pH进行TASK2门控的机制基础尚不清楚。

附:英文原文

Title: Structural basis for pH gating of the two-pore domain K + channel TASK2

Author: Baobin Li, Robert A. Rietmeijer, Stephen G. Brohawn

Issue&Volume: 2020-09-30

Abstract: TASK2 (also known as KCNK5) channels generate pH-gated leak-type K+ currents to control cellular electrical excitability1–3. TASK2 is involved in the regulation of breathing by chemosensory neurons of the retrotrapezoid nucleus in the brainstem4–6 and pH homeostasis by kidney proximal tubule cells7,8. These roles depend on channel activation by intracellular and extracellular alkalization3,8,9, 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.

DOI: 10.1038/s41586-020-2770-2

Source: https://www.nature.com/articles/s41586-020-2770-2

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

分享到:

0