小柯机器人

研究揭示钾离子通道KAT1的机电耦合机制
2020-05-31 15:34

美国芝加哥大学的Eduardo Perozo小组在研究中取得进展。他们的最新工作揭示了钾离子通道KAT1的机电耦合机制。相关论文于2020年5月27日在线发表在《自然》杂志上。

研究人员根据拟南芥的超极化激活电压门控钾(Kv)通道KAT1的低温电子显微镜结构,提出了一种非结构域交换Kv通道中机电耦合和门控极性的分子机制。KAT1显示了一个去极化电压传感器,其直接通过两个界面与封闭的孔隙结构域相互作用,并通过插入的磷脂间接相互作用。
 
在传感器与孔界面处对KAT1结构指导的突变体进行功能评估,研究人员提出了一种机制:传感器与相邻孔亚基中C-接头发夹之间的直接相互作用是门控极性的主要决定因素。研究人员认为,S4传感器螺旋向内运动约5–7Å可以作为直接耦合机制的基础,从而驱动C-接头的构象重新定向并最终打开由S6胞内结构形成的激活门。
 
这种直接耦合机制与超极化激活环状核苷酸门控通道的变构机制相反,并且可能代表了去极化激活通道和超极化激活通道之间的连接。
 
据了解,电压门控钾(Kv)通道通过响应膜去极化或超极化的门控来协调电信号传递并控制细胞体积。但是,尽管电压感应域通过涉及门控电荷向外或向内移位的常见机制来转换跨膜电场,但对通道门控极性的决定因素仍知之甚少。
 
附:英文原文

Title: Electromechanical coupling in the hyperpolarization-activated K + channel KAT1

Author: Michael David Clark, Gustavo F. Contreras, Rong Shen, Eduardo Perozo

Issue&Volume: 2020-05-27

Abstract: Voltage-gated potassium (Kv) channels coordinate electrical signalling and control cell volume by gating in response to membrane depolarization or hyperpolarization. However, although voltage-sensing domains transduce transmembrane electric field changes by a common mechanism involving the outward or inward translocation of gating charges1,2,3, the general determinants of channel gating polarity remain poorly understood4. Here we suggest a molecular mechanism for electromechanical coupling and gating polarity in non-domain-swapped Kv channels on the basis of the cryo-electron microscopy structure of KAT1, the hyperpolarization-activated Kv channel from Arabidopsis thaliana. KAT1 displays a depolarized voltage sensor, which interacts with a closed pore domain directly via two interfaces and indirectly via an intercalated phospholipid. Functional evaluation of KAT1 structure-guided mutants at the sensor–pore interfaces suggests a mechanism in which direct interaction between the sensor and the C-linker hairpin in the adjacent pore subunit is the primary determinant of gating polarity. We suggest that an inward motion of the S4 sensor helix of approximately 5–7 can underlie a direct-coupling mechanism, driving a conformational reorientation of the C-linker and ultimately opening the activation gate formed by the S6 intracellular bundle. This direct-coupling mechanism contrasts with allosteric mechanisms proposed for hyperpolarization-activated cyclic nucleotide-gated channels5, and may represent an unexpected link between depolarization- and hyperpolarization-activated channels.

DOI: 10.1038/s41586-020-2335-4

Source: https://www.nature.com/articles/s41586-020-2335-4

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
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

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