在RTX毒素的乙基化部分中,一个保存的托控制着它们的β2整体素独立的细胞透
Adriana Osickova1, Sarka Knoblochova1, Ladislav Bumba1
1Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic.
The Journal of biological chemistry
|June 30, 2023
概括
像CyaA和HlyA这样的RTX毒素中保存的托芬是透缺乏β2整合素的细胞的关键. 它们的内醇决定了毒素构成,使它们能够独立于整合素结合而进入膜.
科学领域:
- 微生物学和分子生物学
- 蛋白质结构-功能关系 蛋白质结构-功能关系
- 细胞毒理学细胞毒理学
背景情况:
- 重复中毒素 (RTX) 毒素,包括腺酸环酶毒素 (CyaA) 和α-hemolysin (HlyA),与白细胞上的β2整合素结合.
- 这些毒素还可以透到缺乏β2整合素的细胞中,这表明细胞进入的替代机制.
- 在乙化部分内保存的托残留物与毒素活性有关.
研究的目的:
- 为了研究保留的型英醇 (CyaA中的W876,HlyA中的W579) 在β2整合素独立膜透中的作用.
- 阐明这些托残留物对RTX毒素活性的结构和功能影响.
主要方法:
- 保存的托残留物 (CyaA中的W876,HlyA中的W579) 的局部定向突变生成到各种氨基酸.
- 对具有和没有β2整蛋白表达的细胞的毒素活性和细胞毒性的评估.
- 热稳定性测试 (Tm) 和-交换质谱 (HDX-MS) 来探测结构变化.
主要成果:
- W876 (CyaA) 和W579 (HlyA) 的突变损害了β2整合素独立的膜透,同时节省了整合素依赖的活性.
- 这些替代物增加了CyaA的热稳定性,并改变了局部疏水性段的可访问性.
- 在W876中罗利丁-英多尔相互作用的破坏也选择性地损害了红细胞上的CyaA活性.
结论:
- 庞大的W876 (CyaA) 和W579 (HlyA) 的内醇对RTX毒素透至关重要,独立于β2整合素结合.
- 这些残留物调节了乙化环的定位,促进了穿透膜的形状.
- 这些发现揭示了RTX毒素进入细胞的新机制,突出了保存的型的结构性作用.
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