通过对RNF213的酶增强招募来识别基因组学上多样化的病原体
Ana Crespillo-Casado1, Prathyush Pothukuchi1, Katerina Naydenova1
1MRC Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
EMBO reports
|October 7, 2024
概括
E3 泛基因酶RNF213通过形成保护层来结合各种病原体. 这个过程涉及ATP水解和合作性招募,这对于对各种微生物的天生的免疫力至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 天生的免疫力识别了病原体相关的分子模式 (PAMPs) 来检测病原体.
- PAMPs通常是特定于种群的,允许模式识别受体区分不同的微生物.
- 迄今为止,E3无素酶RNF213的宽谱病原体识别机制还未知.
研究的目的:
- 调查RNF213如何识别和响应遗传学上遥远的病原体.
- 阐明RNF213广泛的病原体识别能力背后的结构和功能机制.
主要方法:
- 低温电子显微镜 (cryo-EM) 解析了RNF213的CBM20域的结构.
- 生物化学测试以评估ATP水解和E3结合酶活动的作用.
- 在体外研究分析RNF213在不同病原体上的外层形成.
主要成果:
- RNF213的进化历史表明,它适应了各种病原体结构,特别是在其CBM20域内.
- RNF213在格拉姆阴性细菌 (沙门氏菌),格拉姆阳性细菌 (李斯特菌) 和真核生物 (毒素) 上形成外套.
- ATP水解和RZ指介导的E3结合酶活性对于RNF213层的形成和功能至关重要.
- 层形成是一个由速度限制事件启动的合作过程,而不是简单的扩散.
结论:
- RNF213采用一种独特的酶增强型合作招募机制,以应对进化上遥远的病原体.
- 这种机制使得RNF213能够提供广泛的先天免疫防御,抵御各种微生物威胁.
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