通过膜血激活HssS定义了一个对Staphylococcus aureus中双组分系统信号的范式
Vincent Saillant1, Léo Morey1, Damien Lipuma1
1Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France, Jouy-en-Josas, France.
mBio
|April 29, 2024
概括
黄金葡萄球菌使用HssRS系统来感知和从细胞中去除有毒血红菌. 这项研究揭示了HssS传感器上的血结合部位,这对于激活HrtBA排泄至关重要.
科学领域:
- 微生物学和分子生物学
- 结构生物学 结构生物学
- 病原体与宿主之间的相互作用
背景情况:
- 致病细菌如金黄色葡萄球菌 (Staphylococcus aureus) 面临着管理细胞内血的挑战,血既有毒又必不可少.
- 血质毒性对宿主环境中的细菌构成重大威胁,例如血液流.
- *S. aureus*采用一个由两个组成部分组成的系统,HssRS,通过诱导HrtBA排泄输送器来抵消血毒性.
研究的目的:
- 为了阐明 *S. aureus* HssS 蛋白质的血感应机制.
- 确定与HssS相互作用的结构基础.
- 了解HssS激活如何导致HrtBA血红外流系统的诱导.
主要方法:
- 使用AlphaFold2对HssS二聚体进行结构模拟,然后与heme对接.
- 在HssS中的关键残留物 (Arg94,Arg163,Phe25,Phe128) 的位点定向突变发生.
- 测量野生类型和变种HssS蛋白质的HrtBA合成诱导和血红素结合亲和力的功能测试.
主要成果:
- 一个结构模型揭示了HssS内在膜和细胞外域的接口处的血红素结合部位.
- 保存的细胞外氨酸 (Arg94,Arg163) 和氨酸 (Phe25,Phe128) 对血红蛋白相互作用和HssS激活至关重要.
- 这些残留物中的突变显著损害了HssS功能和血结合,四重突变取消了激活.
结论:
- 外源血在膜/细胞外接口上直接与HssS相互作用,启动HssS激活和随后的HrtBA介导的血挤出.
- 这种"守门人"机制有效地限制了细胞内血红素扩散,保护金黄色菌免受血红素毒性.
- 这些发现为了解病原体血红色感应系统提供了结构和功能基础,并可能为新兴抑制剂的开发提供信息.
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