Nissen-Meyer J, Rogne P, Oppegård C, Haugen H S, Kristiansen P E
Department of Molecular Biosciences, University of Oslo, Oslo, Norway.
Curr Pharm Biotechnol. 2009 Jan;10(1):19-37. doi: 10.2174/138920109787048661.
This review focuses on the structure and mode-of-action of non-lanthionine-containing peptide bacteriocins produced by Gram-positive bacteria. These bacteriocins may be divided into four groups: (i) the anti-listerial one-peptide pediocin-like bacteriocins that have very similar amino acid sequences, (ii) the two-peptide bacteriocins that consist of two different peptides, (iii) the cyclic bacteriocins, and (iv) the linear non-pediocin-like one-peptide bacteriocins. These bacteriocins are largely cationic, contain 20 to 70 residues, and kill cells through membrane-permeabilization. The pediocin-like bacteriocins are the ones that are best characterized. Upon contact with target membranes, their cationic N-terminal half forms a beta-sheet-like structure that binds to the target cell surface, while their more hydrophobic helical-containing C-terminal half penetrates into the hydrophobic core of target-cell membranes and apparently binds to the mannose phosphotransferase permease in a manner that results in membrane leakage. Immunity proteins that protect cells from being killed by pediocin-like bacteriocins bind to the bacteriocin-permease complex and prevent bacteriocin-induced membrane-leakage. Recent structural analyses of two-peptide bacteriocins indicate that they form a helix-helix structure that penetrates into cell membranes. Also these bacteriocins may act by binding to integrated membrane proteins. It is proposed that many membrane-active peptide bacteriocins kill target-cells through basically the same mechanism; the common theme being that a membrane-penetrating part of bacteriocins bind to a membrane embedded region of an integrated membrane protein, thereby causing conformational alterations in the protein that in turn lead to membrane-leakage and cell death.
本综述聚焦于革兰氏阳性菌产生的不含羊毛硫氨酸的肽类细菌素的结构与作用方式。这些细菌素可分为四类：（i）具有非常相似氨基酸序列的抗李斯特菌单肽类片球菌素样细菌素；（ii）由两种不同肽组成的双肽细菌素；（iii）环状细菌素；（iv）线性非片球菌素样单肽细菌素。这些细菌素大多呈阳离子性，含有20至70个残基，并通过使细胞膜通透化来杀死细胞。类片球菌素样细菌素是特征最为明确的一类。与靶细胞膜接触时，其阳离子性的N端一半形成一种β - 折叠样结构，与靶细胞表面结合，而其含更多疏水螺旋的C端一半则穿透进入靶细胞膜的疏水核心，并显然以导致膜渗漏的方式与甘露糖磷酸转移酶通透酶结合。保护细胞免受类片球菌素样细菌素杀伤的免疫蛋白会与细菌素 - 通透酶复合物结合，防止细菌素诱导的膜渗漏。对双肽细菌素的最新结构分析表明，它们形成一种穿透细胞膜的螺旋 - 螺旋结构。这些细菌素也可能通过与整合膜蛋白结合来发挥作用。有人提出，许多具有膜活性的肽类细菌素通过基本相同的机制杀死靶细胞；共同特点是细菌素的膜穿透部分与整合膜蛋白的膜嵌入区域结合，从而导致该蛋白构象改变，进而导致膜渗漏和细胞死亡。
