Bamberg E, Apell H J, Alpes H, Gross E, Morell J L, Harbaugh J F, Janko K, Läuger P
Fed Proc. 1978 Oct;37(12):2633-8.
Channel-forming peptides such as gramicidin A offer the opportunity to study the relationship between chemical structure and transport properties of an ion channel. This article summarizes a number of recent experiments with chemical analogs and derivatives of gramicidin A using artificial lipid bilayer membranes. The introduction of negative charges near the channel mouth leads to an increase in the cation transport rate. Hybrid channels consisting of a neutral and a negatively charged or of a positively and a negatively charged half-channel may be formed. The current-voltage characteristic of these hybrid channels exhibits a pronounced asymmetry. Experiments with charged derivatives of gramicidin A have been used in order to distinguish between different structural models of the dimeric channel; these studies strongly support Urry's model of a single-stranded, head-to-head associated helical dimer. In a further set of experiments gramicidin analogs with modified amino acid sequence were studied. It was found that a single substitution (tryptophan replaced by phenylalanine) leads to marked changes in the conductance of the channel. Analogs with a simplified amino acid sequence such as (L-Trp-D-Leu)7-L-Trp or L-Trp-Gly-(L-Trp-D-Leu)6-L-Trp are able to form cation permeable channels with similar properties as gramicidin A.
诸如短杆菌肽A之类的形成通道的肽为研究离子通道的化学结构与转运特性之间的关系提供了契机。本文总结了近期使用人工脂质双层膜对短杆菌肽A的化学类似物和衍生物进行的一系列实验。在通道口附近引入负电荷会导致阳离子转运速率增加。可能会形成由中性和带负电荷的半通道或带正电荷和带负电荷的半通道组成的混合通道。这些混合通道的电流-电压特性表现出明显的不对称性。对短杆菌肽A的带电衍生物进行的实验已用于区分二聚体通道的不同结构模型；这些研究有力地支持了厄里提出的单链、头对头相连的螺旋二聚体模型。在另一组实验中，研究了氨基酸序列经过修饰的短杆菌肽类似物。发现单一代替（色氨酸被苯丙氨酸取代）会导致通道电导发生显著变化。具有简化氨基酸序列的类似物，如（L-色氨酸-D-亮氨酸）7-L-色氨酸或L-色氨酸-甘氨酸-（L-色氨酸-D-亮氨酸）6-L-色氨酸，能够形成具有与短杆菌肽A相似特性的阳离子通透通道。
