石格拉柔性菌效应物OspI使UBC13脱,以抑制炎症反应
Takahito Sanada1, Minsoo Kim, Hitomi Mimuro
1Department of Infectious Disease Control, International Research Center for Infectious Diseases, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Nature
|March 13, 2012
概括
希格拉柔性菌使用其效应器OspI通过去化UBC13来抑制宿主炎症反应,从而抑制TRAF6信号传递并防止早期感染检测.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
背景情况:
- 细菌病原体侵入宿主细胞,逃避免疫力并通过感知病原体相关分子模式 (PAMPs) 的模式识别受体引起炎症.
- 病原体必须调节宿主炎症信号以在细胞内生存,但细菌在上皮细胞中使用的机制尚不清楚.
- 菌 (Shigella flexneri) 是一种侵入性细菌病原体,可触发宿主免疫反应.
研究的目的:
- 阐明Shigella flexneri调节宿主在上皮细胞入侵时的炎症反应的机制.
- 为了确定参与抑制先天性免疫信号通路的细菌因素.
主要方法:
- 生物化学测试以描述OspI的酶活性.
- 结构生物学技术 (X射线结晶学) 用于确定 OspI 的结构.
- 突变分析以评估催化三合体在OspI功能中的作用.
- 研究OspI对UBC13-TRAF6信号通路的影响.
主要成果:
- 通过抑制TRAF6介导的信号通路,Shigella flexneri效应物OspI可以抑制急性炎症反应.
- OspI是一种谷氨酸脱胺酶,它在谷氨酸100处特异性地脱胺UBC13,抑制其E2无素结合活性.
- OspI 的晶体结构揭示了UBC13 脱化过程中必不可少的催化三元体.
- OspI的目标是UBC13-TRAF6复合体,以调节CBM-TRAF6-NF-κB信号通路.
结论:
- 在感染的早期阶段,Shigella flexneri利用 OspI 抑制宿主炎症反应.
- 针对UBC13-TRAF6相互作用是S. flexneri逃避天生的免疫力的关键策略.
- 了解OspI的机制可以了解细菌病原和宿主-病原体相互作用.
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