肺菌Legionella pneumophila通过一个转谷氨酶活性效应剂调节宿主细胞骨架
Yan Liu1,2, Yao Liu1, Zhao-Qing Luo1
1Department of Biological Sciences, Purdue Institute for Inflammation, Immunology and Infectious Diseases Purdue University West Lafayette Indiana USA.
mLife
|July 2, 2025
概括
肺炎菌使用 RavJ 效应体来交叉连接 Actin 和 Motin 蛋白质,稳定宿主细胞细胞骨架. 这种细菌操纵抑制了actin脱聚合,有助于病原体的生存.
科学领域:
- 微生物学和细胞生物学
- 细菌病原体的产生
- 宿主-病原体相互作用
背景情况:
- 菌利用Dot/Icm IV型分泌系统 (T4SS) 注入超过330种效应蛋白到宿主细胞中.
- 一些效应器修改器官贩运,以建立含有军团菌真空体 (LCV) 的位,用于细胞内复制.
- 主体actin细胞骨架是病原体操纵的关键目标.
研究的目的:
- 研究L. pneumophila效应体RavJ在调节宿主细胞细胞骨架中的作用.
- 阐明RavJ影响actin动态的分子机制.
- 识别与RavJ相互作用的宿主蛋白及其功能后果.
主要方法:
- 确定RavJ是诱导宿主细胞皮质中的F-actin积累的诱因.
- 生物化学测试以证明RavJ的转谷氨酶 (TG) 类活性.
- 质谱和共免疫沉以识别交联蛋白 (actin和Motin家族).
- 对actin-cofilin相互作用和actin脱聚合率的分析.
- 研究RavJ与元效应物LegL1.1之间的相互作用.
主要成果:
- RavJ催化了actin和Motin蛋白质 (例如,Angiomotin,AMOTL1) 之间的共价交联.
- 这种交叉链接发生在AMOT的Gln354残留物上,并抑制了cofilin与actin的结合,从而防止了actin的脱聚合.
- 在L. pneumophila的metaeffectorLegL1直接与RavJ相互作用,对抗其TG活动和减少actin-Motin交叉连接.
结论:
- L. pneumophila使用 RavJ 劫持宿主活性蛋白细胞骨架,通过与Motin蛋白交叉连接活性蛋白来稳定它.
- 这种机制代表了细菌病原体操纵宿主细胞结构并促进细胞内复制的新策略.
- RavJ和LegL1之间的相互作用凸显了L. pneumophila用来控制宿主细胞过程的复杂调节机制.
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