细胞质 GH 环调节磷酰肌醇 4,5-二磷酸诱导的 Kir2 通道门控动力学。
The cytosolic GH loop regulates the phosphatidylinositol 4,5-bisphosphate-induced gating kinetics of Kir2 channels.
机构信息
Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
出版信息
J Biol Chem. 2012 Dec 7;287(50):42278-87. doi: 10.1074/jbc.M112.418640. Epub 2012 Oct 2.
Abstract
Inwardly rectifying K(+) (Kir) channels set the resting membrane potential and regulate cellular excitability. The activity of Kir channels depends critically on the phospholipid PIP(2). The molecular mechanism by which PIP(2) regulates Kir channel gating is poorly understood. Here, we utilized a combination of computational and electrophysiological approaches to discern structural elements involved in regulating the PIP(2)-induced gating kinetics of Kir2 channels. We identify a novel role for the cytosolic GH loop. Mutations that directly or indirectly affect GH loop flexibility (e.g. V223L, E272G, D292G) increase both the on- and especially the off-gating kinetics. These effects are consistent with a model in which competing interactions between the CD and GH loops for the N terminus regulate the gating of the intracellular G loop gate.
摘要
内向整流钾 (Kir) 通道设定静息膜电位并调节细胞兴奋性。Kir 通道的活性严重依赖于磷脂 PIP(2)。然而，PIP(2)调节 Kir 通道门控的分子机制仍知之甚少。在这里，我们利用计算和电生理方法的组合来辨别参与调节 Kir2 通道的 PIP(2)诱导门控动力学的结构元件。我们确定了胞质 GH 环的一个新作用。直接或间接影响 GH 环灵活性的突变（例如 V223L、E272G、D292G）增加了开启和关闭门控动力学。这些效应与一个模型一致，即 CD 和 GH 环对 N 端的竞争相互作用调节细胞内 G 环门的门控。
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