AMOEBAPORES, A FAMILY OF MEMBRANOLYTIC PEPTIDES FROM CYTOPLASMIC GRANULES OF ENTAMOEBA-HISTOLYTICA - ISOLATION, PRIMARY STRUCTURE, AND PORE FORMATION IN BACTERIAL CYTOPLASMIC MEMBRANES
AMOEBAPORES, A FAMILY OF MEMBRANOLYTIC PEPTIDES FROM CYTOPLASMIC GRANULES OF ENTAMOEBA-HISTOLYTICA - ISOLATION, PRIMARY STRUCTURE, AND PORE FORMATION IN BACTERIAL CYTOPLASMIC MEMBRANES
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DOI：
10.1111/j.1365-2958.1994.tb01325.x
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发表时间：
1994-12-01
影响因子：
3.6
通讯作者：
MULLEREBERHARD, HJ
中科院分区：
文献类型：
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作者：
LEIPPE, M;ANDRA, J;MULLEREBERHARD, HJ
通过酸提取、凝胶过滤和反相高效液相色谱分离，从致病性溶组织内阿米巴胞质颗粒中分离出3个具有成孔活性的多肽，对3个活性多肽进行部分氨基酸序列分析，结果表明，其中最丰富的是阿米巴，另外两个是其异构体。基因组DNA的克隆和测序解析了这两个新发现的多肽的氨基酸序列。这三个被命名为变形虫A、B和C的多肽被发现具有相同的分子大小，但其一级结构明显不同，尽管所有六个半胱氨酸残基都是保守的。尽管序列不同，但结构含义预测这三个肽都有类似的由二硫键稳定的两亲性α-螺旋构象。三种异构体对脂泡均显示出造孔活性，但动力学有所不同。它们还能够扰乱细菌细胞膜的完整性，从而杀死革兰氏阳性细菌。变形虫代表了一个不同的膜活性多肽家族，它们可以作为细胞内的抗菌剂发挥作用，但也可以赋予寄生虫细胞溶解活性。
Three peptides with pore-forming activity were isolated from the cytoplasmic granules of pathogenic Entamoeba histolytica by acidic extraction, gel filtration and reversed-phase high-performance liquid chromatography, Partial amino acid sequence analysis of the three active peptides revealed that the most abundant of them was amoebapore and the other two were isoforms thereof. Cloning and sequencing of genomic DNA resolved the amino acid sequence of the two newly recognized peptides. The three peptides designated amoebapores A, B and C were found to have the same molecular size but to differ markedly in their primary structure, although all six cysteine residues are conserved. Despite sequence divergence, structural implications predict for the three peptides a similar amphipathic a-helical conformation stabilized by disulphide bonds. AII three isoforms exhibit pore-forming activity toward lipid vesicles, but they differ in their kinetics. They also are capable of perturbing the integrity of bacterial cytoplasmic membranes and thereby kill Grampositive bacteria. The amoebapores represent a distinct family of membrane-active peptides that may function intracellularly as antimicrobial agents but may also confer cytolytic activity on the parasite.