Amino acid substitutions and ion channel function. Model-dependent conclusions.
Amino acid substitutions and ion channel function. Model-dependent conclusions.
复制标题
氨基酸取代和离子通道功能。
DOI：
10.1016/s0006-3495(92)81767-8
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发表时间：
1992
影响因子：
3.4
通讯作者：
Andersen,OS
中科院分区：
文献类型：
--
作者：
Becker,MD;Koeppe2nd,RE;Andersen,OS
当结合分子生物学和电生理学方法来研究通道功能时，出现了两个问题：突变体和天然通道在结构上是等同的吗？Durkin等人，1990），这样一个sequencealteration可以被视为一个”点扰动”（这通常是一个先决条件的机制分析）;和，如果答案是肯定的，什么是一个适当的分子解释的功能改变？这些研究中的母体化合物[Val ′]短杆菌肽A（gA）具有以下序列：甲酰-L-Val ′-Gly 2-L-Ala 3-D-Leu 4-L-Ala 5-D-Val 6-L-Val 7-D-Val 8-L-Trp 9-D-Leu 10-L-Trp ′ l-D-Leu ′ 2-L-Trp 13-D-Leu 14-L-Trp ′ 5-乙醇胺。交替的L，D序列允许gA形成通道，这些通道是B63-螺旋的甲酰基-NH-至-甲酰基-NH二聚体（分子内螺旋，其中肽基团排列在孔中，而侧链形成外表面）。
Two questions arise when molecular biological and electrophysiological methods are combined to study channel function: are the mutant and native channels structurally equivalent (cf. Durkin et al., 1990), such that a sequencealteration can be regarded as a" point perturbation"(which usually will be a prerequisite for mechanistic analysis); and, if the answer is affirmative, what is an appropriate molecular interpretation of the functional alterations? We will address the latter question.The parent compound in these studies,[Val'] gramicidin A (gA), has thesequence: Formyl-L-Val'-Gly2-L-Ala3-D-Leu4-L-Ala5-D-Val6-L-Val7-D-Val8-L-Trp9-D-Leu10-L-Trp'l-D-Leu'2-L-Trp13-D-Leu14-L-Trp'5-ethanolamine. The alter-nating L, D sequence permits gA to form channels that are Formyl-NH-to-Formyl-NH dimers of, B63-helices (in-tramolecular helices, in which the peptide groups line the pore whereas the side chains form the exterior surface).