Rim domain loops of Staphylococcal β-pore forming bi-component toxin S-components recognize target human erythrocytes in a coordinated manner.
Rim domain loops of Staphylococcal β-pore forming bi-component toxin S-components recognize target human erythrocytes in a coordinated manner.
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葡萄球菌 β 孔形成双组分毒素 S 组分的边缘结构域环以协调的方式识别目标人类红细胞。
DOI：
10.1093/jb/mvy030
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Kaneko J.
中科院分区：
文献类型：
--
作者：
Peng Z;Takeshita M;Shibata N;Tada H;Tanaka Y;Kaneko J.
金黄色葡萄球菌双组分成孔毒素由S-和F-组分组成，并在靶血细胞膜上形成异八聚体β-桶孔。其中，γ-溶血素（Hlg 2和Luk的F组分（LukF））和LukED（LukE和LukD）具有溶血活性，而Panton-Valentine杀白细胞素（LukS-PV和LukF-PV）不裂解人红细胞。在此，我们重点研究了S-组分边缘结构域中的四个环结构，即环-1、环-2、环-3和环-4，并发现用LukS-PV的环取代Hlg 2和LukE中的环-4可以消除它们的溶血活性。此外，LukS-PV通过与Hlg 2或LukE的Loop-4交换获得溶血活性，表明这些S-组分的Loop-4决定红细胞特异性。LOOP-1和-2增强了两种组分的红细胞结合能力。虽然Hlg 2和LukE识别人红细胞上的趋化因子的Duffy抗原受体，但是Loop-4的能力在Hlg 2和LukE之间不是互补的。与LukE Loop-4交换的Hlg 2显示比完整的Hlg 2更弱的活性，并且具有Hlg 2 Loop-4的LukE突变体在与LukD的组合中失去其溶血活性。有趣的是，这些Loop-4交换突变体的溶血活性受到F组分的影响，即LukF增强了这些Hlg 2和LukE Loop-4突变体的溶血活性，以及LukS-PV突变体与LukE Loop-4的溶血活性。
Staphylococcus aureusbi-component pore-forming toxins consist of S- and F-components, and form hetero-octameric beta-barrel pores on target blood cell membranes. Among them, γ-haemolysin (Hlg2 and F-component of Luk (LukF)) and LukED (LukE and LukD) possess haemolytic activity, whereas the Panton-Valentine leukocidin (LukS-PV and LukF-PV) does not lyse human erythrocytes. Here, we focussed on four loop structures in the rim domain of S-component, namely loops -1, -2, -3 and -4, and found that replacement of Loop-4 in both Hlg2 and LukE with that of LukS-PV abolished their haemolytic activity. Furthermore, LukS-PV gained haemolytic activity by Loop-4 exchange with Hlg2 or LukE, suggesting that Loop-4 of these S-components determined erythrocyte specificity. LOOP-1 and -2 enhanced the erythrocytes-binding ability of both components. Although Hlg2 and LukE recognize Duffy antigen receptor for chemokines on human erythrocytes, the ability of Loop-4 was not complementary between Hlg2 and LukE. Exchange of Hlg2 with LukE Loop-4 showed weaker activity than intact Hlg2, and LukE mutant with Hlg2 Loop-4 lost its haemolytic activity in combination of LukD. Interestingly, the haemolytic activities of these Loop-4 exchange mutants were affected by F-component, namely LukF enhanced haemolytic activities of these Hlg2 and LukE Loop-4 mutants, and also haemolytic activity of LukS-PV mutant with LukE Loop-4.