Bacterial Two-component and Hetero-heptameric Pore-forming Cytolytic Toxins : Structures, Pore-forming Mechanism

葡萄球菌γ-溶血素（Hlg）、杀白细胞素（Luk）和Panton-Valentine杀白细胞素（PVL）是最早在细菌中发现的双组分异源寡聚成孔溶细胞毒素（或溶细胞素）。迄今为止，除葡萄球菌菌株外，没有关于细菌中存在异源寡聚成孔溶细胞毒素的信息。Hlg（34 kDa的Hlg 1/32 kDa的Hlg 2）有效地溶解来自人类和其他哺乳动物物种的红细胞。Luk（34 kDa的LukF/33 kDa的LukS）对人和兔多形核白细胞和兔红细胞具有细胞溶解性，PVL（34 kDa的LukF-PV/33 kDa的LukS-PV）显示出对白细胞具有高细胞特异性的细胞溶解活性。Hlg 1与LukF相同，溶细胞素的细胞特异性由Hlg 2和LukS决定。基于毒素组分的一级和三维结构，认为Hlg、Luk和PVL。最近，我们的研究使用单分子荧光成像技术首次阐明了LukF和Hlg 2单体在人红细胞膜上组装成Hlg的成孔异源寡聚体的机制。我们估计了11个连续的平衡常数的组装途径，其中包括开始与膜结合的单体，通过单孔寡聚化的收益，并最终在形成集群的孔。

Staphylococcal γ-hemolysin (Hlg), leukocidin (Luk), and Panton-Valentine leukocidin (PVL) are two-component and hetero-oligomeric pore-forming cytolytic toxins (or cytolysin), that were first identified in bacteria. No information on the existence of hetero-oligomeric pore-forming cytolytic toxins in bacteria except for staphylococcal strains is available so far. Hlg (Hlg1 of 34 kDa/Hlg2 of 32 kDa) effectively lyses erythrocytes from human and other mammalian species. Luk (LukF of 34 kDa/LukS of 33 kDa) is cytolytic toward human and rabbit polymorphonuclear leukocytes and rabbit erythrocytes, and PVL (LukF-PV of 34 kDa/LukS-PV of 33 kDa) reveals cytolytic activity with a high cell specificity to leukocytes. Hlg1 is identical to LukF and that the cell specificities of the cytolysins are determined by Hlg2 and LukS. Based on the primary and 3-dimensional structures of the toxin components, Hlg, Luk, and PVL are thought. to form a family of proteins.Recently, the assembly mechanism of the LukF and Hlg2 monomers into pore-forming hetero-oligomers of Hlg on human erythrocyte membranes has been clarified for the first time by our study using a single-molecular fluorescence imaging technique. We estimated 11 sequential equilibrium constants for the assembly pathway which includes the beginning with membrane binding of monomers, proceeds through single pore oligomerization, and culminates in the formation of clusters of the pores.