Structural consequences of anesthetic and nonimmobilizer interaction with gramicidin A channels.
Structural consequences of anesthetic and nonimmobilizer interaction with gramicidin A channels.
复制标题
麻醉剂和非固定剂与短杆菌肽 A 通道相互作用的结构后果。
DOI：
10.1016/s0006-3495(99)77391-1
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发表时间：
1999
影响因子：
3.4
通讯作者：
Xu,Y
中科院分区：
文献类型：
--
作者：
Tang,P;Simplaceanu,V;Xu,Y
虽然已经研究了全身麻醉剂与可溶性蛋白质的相互作用，但是与表征全身麻醉的膜结合蛋白质的特异性相互作用在很大程度上是未知的。麻醉剂与突触离子通道相互作用的结构调节尚未阐明。使用短杆菌肽A作为跨膜离子通道的简化模型，我们最近证明了一对结构相似的挥发性麻醉剂和非固定剂，1-氯-1，2，2-三氟环丁烷（F3）和1，2-二氯六氟环丁烷（F6），分别对通道功能有明显不同的影响。使用高分辨率的NMR结构分析，我们在这里表明，无论是F3或F6的相关浓度可以显着影响短杆菌肽A通道的二级结构。虽然麻醉剂F3和nonimmobilizer F6可以扰动残基在中间部分的通道深处的疏水区域内的十二烷基硫酸钠胶束，只有F3，而不是F6，可以显着改变附近的通道入口的色氨酸吲哚N-H质子的化学位移。结果与麻醉剂通过与肽-脂-水界面处的两亲结构域相互作用而引起通道功能改变的观点一致。
Although interactions of general anesthetics with soluble proteins have been studied, the specific interactions with membrane bound-proteins that characterize general anesthesia are largely unknown. The structural modulations of anesthetic interactions with synaptic ion channels have not been elucidated. Using gramicidin A as a simplified model for transmembrane ion channels, we have recently demonstrated that a pair of structurally similar volatile anesthetic and nonimmobilizer, 1-chloro-1,2,2-trifluorocyclobutane (F3) and 1,2-dichlorohexafluorocyclobutane (F6), respectively, have distinctly different effects on the channel function. Using high-resolution NMR structural analysis, we show here that neither F3 nor F6 at pharmacologically relevant concentrations can significantly affect the secondary structure of the gramicidin A channel. Although both the anesthetic F3 and the nonimmobilizer F6 can perturb residues at the middle section of the channel deep inside the hydrophobic region in the sodium dodecyl sulfate micelles, only F3, but not F6, can significantly alter the chemical shifts of the tryptophan indole N-H protons near the channel entrances. The results are consistent with the notion that anesthetics cause functional change of the channel by interacting with the amphipathic domains at the peptide-lipid-water interface.