Cation-Selective Channel Regulated by Anions According to Their Hofmeister Ranking.

Cation-Selective Channel Regulated by Anions According to Their Hofmeister Ranking.
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DOI:
10.1002/anie.201611335
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发表时间:
2017-03-20
期刊:
Angewandte Chemie (International ed. in English)
影响因子:
--
通讯作者:
Bezrukov SM
Bezrukov SM
中科院分区:
其他
文献类型:
--
作者:
Gurnev PA;Roark TC;Petrache HI;Sodt AJ;Bezrukov SM

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小离子的特异性,霍夫迈斯特排名,早已为人所知,并有许多应用,包括医学。然而,它回避了一致的理论描述。本文研究了霍夫迈斯特阴离子对脂质膜中革兰草毒素A通道的影响。与直觉相反,我们发现在H2PO4−<Cl−≈Br−≈NO3−<ClO4−<SCN−系列中,这种完美的阳离子选择性通道的电导增加了大约两倍。通道解离动力学表现出更强的依赖性,停留时间增加约20倍。虽然电导率可以通过膜表面电位的变化来定量解释,这是由于从表面排除了宇宙异向物(或在表面积聚了混沌异向物),但动力学证明更难处理。我们估计了双分子层表面能量学变化对通道停留时间的影响,得出的结论是,这种变化必须大于通常在脂质双分子层外观察到的霍夫迈斯特效应。离子特异性,特别是阴离子在盐诱导蛋白质沉淀中的独特作用,自19世纪80年代以来就已为人所知,当时弗朗茨·霍夫迈斯特(Franz Hofmeister)建立了阴离子调节蛋黄蛋白水溶性能力的排名。实验和理论研究已经给出了这一现象的详细经验图像,但导致霍夫迈斯特效应的离子与表面相互作用的性质仍在争论中。唯一的共识是它不能用电解质的标准理论来解释。例如,溴化物的独特之处在于,它的盐在霍夫迈斯特的研究之前几十年就被认为是一种治疗癫痫的药物,它们仍然被用于治疗特定类型的儿童难治性癫痫发作,但它们的作用机制仍然难以捉摸。中性脂质膜纳米孔的霍夫迈斯特效应研究。出乎意料的是,我们发现纯阳离子选择性肽孔的电导是由阴离子调节的,与它们在Hofmeister系列中的位置相关。此外,孔隙构象动力学对阴离子种类高度敏感。我们将这两种效应与膜-水界面上向宇宙性阴离子的优先耗竭(向混沌性阴离子的积累)联系起来。
Specificity of small ions, the Hofmeister ranking, is long-known and has many applications including medicine. Yet it evades consistent theoretical description. Here we study the effect of Hofmeister anions on gramicidin A channels in lipid membranes. Counterintuitively, we find that conductance of this perfectly cation-selective channel increases about two-fold in the H2PO4−<Cl−≈Br−≈NO3−<ClO4−<SCN− series. Channel dissociation kinetics show even stronger dependence, with the dwell time increasing ~20-fold. While the conductance can be quantitatively explained by the changes in membrane surface potential due to exclusion of kosmotropes from (or accumulation of chaotropes at) the surface, the kinetics proved to be more difficult to treat. We estimate the effects of changes in the energetics at the bilayer surfaces on the channel dwell time, concluding that the change would have to be greater than typically observed for the Hofmeister effect outside the context of the lipid bilayer. Ion specificity and, in particular, the distinctive effects of anions in salt-induced protein precipitation have been known since the 1880’s, when Franz Hofmeister established the ranking of anions in their ability to regulate egg yolk protein water solubility . Experimental and theoretical studies have given a detailed empirical picture of the phenomenon, the nature of the ionic interactions with the surfaces leading to the Hofmeister effect is still under debate . The only consensus is that it cannot be explained by standard theories of electrolytes. For example, bromide is unique in that its salts were recognized as a drug to treat epilepsy a couple of dozen years before Hofmeister’s studies and they are still in use to treat specific types of refractory seizures in children , but the mechanism of their action remains elusive. Hofmeister effect studied with a nanopore in a neutral lipid membrane. Rather unexpectedly, we find that conductance of a purely cation-selective peptide pore is regulated by anions in correlation with their position in the Hofmeister series. Moreover, the pore conformational dynamics are highly sensitive to the anion species. We relate both effects to preferential depletion of kosmotropic anions (accumulation of chaotropic anions) at the membrane-water interface.
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