Latal A, Degovics G, Epand R F, Epand R M, Lohner K
Institut für Biophysik und Röntgenstrukturforschung, Osterreichische Akademie der Wissenschaften, Graz, Austria.
Eur J Biochem. 1997 Sep 15;248(3):938-46. doi: 10.1111/j.1432-1033.1997.00938.x.
The interaction of PGLa (peptidyl-glycylleucine-carboxyamide), a 21-amino-acid residue cationic peptide, isolated from the skin of the South African clawed frog, Xenopus laevis, with model membrane systems was investigated. Our studies focussed on the importance of the difference in the phospholipid composition of bacterial and erythrocyte membranes. This is of particular interest to gain information on the specificity of membranolysis exhibited by this peptide against bacteria but not against erythrocytes. In phosphate buffer at physiological pH, as well as in the presence of the zwitterionic phosphatidylcholine and sphingomyelin. the peptide had a random structure but it adopted an alpha-helical conformation in the presence of negatively charged lipids. Furthermore, calorimetric experiments showed that PGLa had no effects on the thermotropic phase behavior of liposomes composed of the choline phosphatides, while separation of a distinct peptide-rich domain was observed for phosphatidylglycerol liposomes. In addition to the main transition of pure 1,2-dipalmitoylglycerophosphoglycerol at 40 degrees C a second transition owing to the peptide-perturbed lipid domains was found at 41 degrees C. This conclusion is supported by X-ray diffraction experiments which indicated that PGLa penetrates into the hydrophobic core of the bilayer inducing an untilting of the hydrocarbon chains as observed in the gel phase of the pure lipid. These results demonstrate that this antibacterial peptide specifically interacts with negatively charged lipid membranes, which are characteristic of bacterial membranes. This can be explained based on the structural features of PGLa.
对从南非爪蟾（非洲爪蟾）皮肤中分离出的含21个氨基酸残基的阳离子肽PGLa（肽基 - 甘氨酰 - 亮氨酸 - 羧酰胺）与模型膜系统的相互作用进行了研究。我们的研究集中在细菌膜和红细胞膜磷脂组成差异的重要性上。这对于获取有关该肽对细菌而非红细胞表现出的膜溶解特异性的信息尤为重要。在生理pH值的磷酸盐缓冲液中，以及在两性离子磷脂酰胆碱和鞘磷脂存在的情况下，该肽具有无规结构，但在带负电荷的脂质存在时会采用α - 螺旋构象。此外，量热实验表明，PGLa对由胆碱磷脂组成的脂质体的热致相行为没有影响，而对于磷脂酰甘油脂质体则观察到一个明显的富含肽的结构域的分离。除了在40℃时纯二棕榈酰甘油磷脂酰甘油的主要转变外，在41℃时还发现了由于肽扰动脂质结构域引起的第二次转变。X射线衍射实验支持了这一结论，该实验表明PGLa穿透到双层膜的疏水核心中，导致烃链如在纯脂质的凝胶相中观察到的那样发生倾斜。这些结果表明，这种抗菌肽与带负电荷的脂质膜特异性相互作用，而带负电荷的脂质膜是细菌膜的特征。这可以根据PGLa的结构特征来解释。
