Koeppe R E, Providence L L, Greathouse D V, Heitz F, Trudelle Y, Purdie N, Andersen O S
Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville 72701.
Proteins. 1992 Jan;12(1):49-62. doi: 10.1002/prot.340120107.
In order to resolve whether gramicidin A channels are formed by right- or left-handed beta-helices, we synthesized an optically reversed (or mirror image) analogue of gramicidin A, called gramicidin A-, to test whether it forms channels that have the same handedness as channels formed by gramicidin M- (F. Heitz et al., Biophys. J. 40:87-89, 1982). In gramicidin M- the four tryptophan residues have been replaced with phenylalanine, and the circular dichroism (CD) spectrum therefore reflects almost exclusively contributions from the polypeptide backbone. The CD spectrum of gramicidin M- in dimyristoylphosphatidylcholine vesicles is consistent with a left-handed helical backbone folding motif (F. Heitz et al., Biophys. Chem. 24:149-160, 1986), and the CD spectra of gramicidins A and A- are essentially mirror images of each other. Based on hybrid channel experiments, gramicidin A- and M- channels are structurally equivalent, while gramicidin A and A- channels are nonequivalent, being of opposite helix sense. Gramicidin A- channels are therefore left-handed, and natural gramicidin A channels in phospholipid bilayers are right-handed beta 6.3-helical dimers.
为了确定短杆菌肽A通道是由右手还是左手β-螺旋形成的，我们合成了一种短杆菌肽A的光学反转（或镜像）类似物，称为短杆菌肽A-，以测试它形成的通道是否与短杆菌肽M-形成的通道具有相同的手性（F. 海茨等人，《生物物理学杂志》40:87 - 89，1982年）。在短杆菌肽M-中，四个色氨酸残基已被苯丙氨酸取代，因此圆二色性（CD）光谱几乎完全反映了多肽主链的贡献。短杆菌肽M-在二肉豆蔻酰磷脂酰胆碱囊泡中的CD光谱与左手螺旋主链折叠基序一致（F. 海茨等人，《生物物理化学》24:149 - 160，1986年），并且短杆菌肽A和A-的CD光谱基本上是彼此的镜像。基于混合通道实验，短杆菌肽A-和M-通道在结构上是等效的，而短杆菌肽A和A-通道是不等效的，具有相反的螺旋方向。因此，短杆菌肽A-通道是左手性的，并且磷脂双层中的天然短杆菌肽A通道是右手性β6.3-螺旋二聚体。
