Interface connections of a transmembrane voltage sensor
Interface connections of a transmembrane voltage sensor
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DOI：
10.1073/pnas.0507618102
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发表时间：
2005-10-18
影响因子：
11.1
通讯作者：
White, SH
中科院分区：
文献类型：
--
作者：
Freites, JA;Tobias, DJ;White, SH
电压敏感离子通道会根据 S4 电压传感器运动引起的跨膜 (TM) 电位变化而打开和关闭。这些传感器是α-螺旋，包含四个或更多带正电的氨基酸，最常见的是精氨酸。所谓的桨模型，基于 KvAP K+ 通道的高分辨率结构 [Jiang, et al (2003) Nature 423, 33-41]，假设 S4 传感器响应 TM 电压变化而在膜双层内移动。 S4 传感器直接暴露于脂质与传统预期相反，传统预期是膜碳氢化合物核心和水之间的介电对比对电荷埋藏造成了不可克服的能量损失。然而，最近的实验表明，具有 KvAP S4 序列的螺旋可以插入内质网膜。为了使这一结果与经典能量学论证相一致，我们对脂质双层中的孤立 TM S4 螺旋进行了分子动力学模拟。模拟揭示了精氨酸周围水和脂质磷酸盐的稳定氢键网络，该网络将双层碳氢化合物核心的有效厚度减少到螺旋附近的大约 10 埃。这表明双层磷脂可以局部适应强烈扰动的蛋白质元素，导致磷脂成为蛋白质的结构延伸。
Voltage-sensitive ion channels open and close in response to changes in transmembrane (TM) potential caused by the motion of the S4 voltage sensors. These sensors are a-helices that include four or more positively charged amino acids, most commonly arginine. The so-called paddle model, based on the high-resolution structure of the KvAP K+ channel [Jiang, et al (2003) Nature 423, 33-41], posits that the S4 sensors move within the membrane bilayer in response to TM voltage changes. Direct exposure of S4 sensors to lipid is contrary to the classical expectation that the dielectric contrast between the membrane hydrocarbon core and water presents an insurmountable energetic penalty to burial of electric charges. Nevertheless, recent experiments have shown that a helix with the sequence of KvAP S4 can be inserted across the endoplasmic reticulum membrane. To reconcile this result with the classical energetics argument, we have carried out a molecular dynamics simulation of an isolated TM S4 helix in a lipid bilayer. The simulation reveals a stabilizing hydrogen-bonded network of water and lipid phosphates around the arginines that reduces the effective thickness of the bilayer hydrocarbon core to approximate to 10 angstrom in the vicinity of the helix. It suggests that bilayer phospholipids can adapt locally to strongly perturbing protein elements, causing the phospholipids to become a structural extension of the protein.