Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo, Edificio Santiago Gascón, Campus de El Cristo, 33006 Oviedo, Asturias, Spain.
Oncophysiology Group, Max Planck Institute of Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen, Germany.
Int J Mol Sci. 2019 Jan 10;20(2):248. doi: 10.3390/ijms20020248.
Voltage-dependent potassium channels (Kv channels) are crucial regulators of cell excitability that participate in a range of physiological and pathophysiological processes. These channels are molecular machines that display a mechanism (known as gating) for opening and closing a gate located in a pore domain (PD). In Kv channels, this mechanism is triggered and controlled by changes in the magnitude of the transmembrane voltage sensed by a voltage-sensing domain (VSD). In this review, we consider several aspects of the VSD⁻PD coupling in Kv channels, and in some relatives, that share a common general structure characterized by a single square-shaped ion conduction pore in the center, surrounded by four VSDs located at the periphery. We compile some recent advances in the knowledge of their architecture, based in cryo-electron microscopy (cryo-EM) data for high-resolution determination of their structure, plus some new functional data obtained with channel variants in which the covalent continuity between the VSD and PD modules has been interrupted. These advances and new data bring about some reconsiderations about the use of exclusively a classical electromechanical lever model of VSD⁻PD coupling by some Kv channels, and open a view of the Kv-type channels as allosteric machines in which gating may be dynamically influenced by some long-range interactional/allosteric mechanisms.
电压门控钾通道（Kv 通道）是细胞兴奋性的关键调节因子，参与多种生理和病理生理过程。这些通道是分子机器，具有一种开启和关闭位于孔域（PD）中的门的机制（称为门控）。在 Kv 通道中，这种机制由通过电压感应域（VSD）感知的跨膜电压的幅度变化触发和控制。在这篇综述中，我们考虑了 Kv 通道及其某些相关通道中 VSD⁻PD 偶联的几个方面，这些通道具有共同的一般结构，其特征是中心有一个正方形的离子传导孔，周围有四个位于外围的 VSD。我们根据低温电子显微镜（cryo-EM）数据编译了一些关于其结构的最新进展，这些数据用于高分辨率地确定其结构，以及一些使用 VSD 和 PD 模块之间的共价连续性被中断的通道变体获得的新功能数据。这些进展和新数据促使人们重新考虑某些 Kv 通道仅使用经典的电机械杠杆模型来解释 VSD⁻PD 偶联，同时也为 Kv 型通道作为变构机器提供了一种观点，在这种机器中，门控可能会受到某些远程相互作用/变构机制的动态影响。
