PDF(Pubmed)
Abstract：
Perturbations in bilayer material properties (thickness, lipid intrinsic curvature and elastic moduli) modulate the free energy difference between different membrane protein conformations, thereby leading to changes in the conformational preferences of bilayer-spanning proteins. To further explore the relative importance of curvature and elasticity in determining the changes in bilayer properties that underlie the modulation of channel function, we investigated how the micelle-forming amphiphiles Triton X-100, reduced Triton X-100 and the HII lipid phase promoter capsaicin modulate the function of alamethicin and gramicidin channels. Whether the amphiphile-induced changes in intrinsic curvature were negative or positive, amphiphile addition increased gramicidin channel appearance rates and lifetimes and stabilized the higher conductance states in alamethicin channels. When the intrinsic curvature was modulated by altering phospholipid head group interactions, however, maneuvers that promote a negative-going curvature stabilized the higher conductance states in alamethicin channels but destabilized gramicidin channels. Using gramicidin channels of different lengths to probe for changes in bilayer elasticity, we found that amphiphile adsorption increases bilayer elasticity, whereas altering head group interactions does not. We draw the following conclusions: first, confirming previous studies, both alamethicin and gramicidin channels are modulated by changes in lipid bilayer material properties, the changes occurring in parallel yet differing dependent on the property that is being changed; second, isolated, negative-going changes in curvature stabilize the higher current levels in alamethicin channels and destabilize gramicidin channels; third, increases in bilayer elasticity stabilize the higher current levels in alamethicin channels and stabilize gramicidin channels; and fourth, the energetic consequences of changes in elasticity tend to dominate over changes in curvature.
摘要：
双层材料属性的扰动(厚度，脂质固有曲率和弹性模量）调节不同膜蛋白构象之间的自由能差异，从而导致跨双层蛋白构象偏好的变化。为了进一步探索曲率和弹性在确定作为通道功能调节基础的双层属性变化中的相对重要性，我们研究了形成胶束的两亲物TritonX-100，减少的TritonX-100和HII脂相启动子辣椒素如何调节阿米霉素和小草菌素通道的功能。两亲物诱导的固有曲率变化是负的还是正的，两亲物的添加增加了小草菌素通道的出现率和寿命，并稳定了alamethicin通道中的较高电导状态。当通过改变磷脂头基相互作用来调节固有曲率时，然而,促进负向曲率的动作稳定了阿米西星通道中的较高电导状态，但不稳定了克霉菌素通道。利用不同长度的小麦草素通道探测双层弹性的变化,我们发现两亲物吸附增加了双层弹性，而改变头组相互作用则没有。我们得出以下结论:第一,证实了以前的研究，阿米霉素和小草菌素通道都受到脂质双层材料特性变化的调节，并行发生但不同的变化取决于被改变的属性；第二，孤立的,曲率的负向变化使阿米他星通道中的较高电流水平稳定，并使他汀通道不稳定；第三，双层弹性的增加稳定了阿米希星通道中更高的电流水平，并稳定了克霉菌素通道；第四，弹性变化的能量后果倾向于主导曲率的变化。
