Brachais L, Davoust D, Molle G
URA 500 CNRS, University of Rouen, Faculty of Science, Mount-Saint-Aignan, France.
Int J Pept Protein Res. 1995 Feb;45(2):164-72. doi: 10.1111/j.1399-3011.1995.tb01036.x.
Alamethicin, a 20-residue peptaibol, induces voltage-dependent ion channels in lipid bilayers according to the barrel-stave model. A synthetic analogue (L2) in which all Aib were replaced by Leu shows a conductance behaviour similar to alamethicin, but channel lifetimes are drastically reduced. Among several hypotheses, a different conformation for L2 might be responsible for this phenomenon by increasing the alpha-helical content (alamethicin presents some 3.0(10)-helical parts) and thus decreasing the length of the transmembrane part. A conformational study of L2 was undertaken using FTIR, CD and NMR spectroscopy, and the secondary structure was compared with alamethicin. These techniques showed an enhanced predominant helical structure as compared to alamethicin. Moreover, the NOE pattern showed an exclusively alpha-helical conformation, resulting in a smaller length of the L2 peptide. This shortening somewhat impedes the complete crossing of the membrane, and could then explain the reduction of its ion-channel lifetimes.
短杆菌肽A是一种由20个氨基酸残基组成的肽抗生素，根据桶板模型，它能在脂质双分子层中诱导电压依赖性离子通道。一种将所有Aib替换为Leu的合成类似物（L2）表现出与短杆菌肽A相似的电导行为，但通道寿命大幅缩短。在几种假设中，L2不同的构象可能是导致这种现象的原因，它通过增加α-螺旋含量（短杆菌肽A呈现约3.0(10)-螺旋部分）从而缩短跨膜部分的长度。利用傅里叶变换红外光谱、圆二色光谱和核磁共振光谱对L2进行了构象研究，并将其二级结构与短杆菌肽A进行了比较。这些技术表明，与短杆菌肽A相比，L2的主要螺旋结构增强。此外，核Overhauser效应图谱显示L2具有完全的α-螺旋构象，导致L2肽的长度较短。这种缩短在一定程度上阻碍了其完全穿过膜，进而可以解释其离子通道寿命的缩短。
