宏观域含有Thoeris抗菌体防御系统的结构特征
Yun Shi1, Veronika Masic1, Tamim Mosaiab1
1Institute for Glycomics, Griffith University, Southport, QLD 4222, Australia.
Science advances
|June 26, 2024
概括
托埃里斯的防御系统使用不同的ThsA效应机制来保护细菌免受菌体的侵害. 这项研究揭示了含有ThsA蛋白质的跨膜和宏域 (TM-宏) 如何通过独特的核酸信号通路触发流产性感染.
科学领域:
- 菌体的防御机制 菌体的防御机制
- 细菌免疫的分子生物学
- 在 prokaryotes 中的信号转导.
背景情况:
- 托埃里斯的防御系统通过流产性感染为细菌提供对菌体的免疫力.
- ThsB蛋白感知菌体感染,并使用信号核酸激活ThsA效应器.
- 现有的Thoeris系统使用SIR2-SLOG ThsA效应器,由特定的循环ADP-ribose (cADPR) 异构体激活,导致尼古丁胺胺腺因二核酸 (NAD+) 耗尽.
研究的目的:
- 描述采用含有ThsA效应器的跨膜和宏域 (TM-宏) 的Thoeris系统.
- 阐明TM-宏ThsA蛋白的核酸结合和激活机制.
- 为了比较SIR2-SLOG和TM-宏ThsA效应器在细菌防御中的机制.
主要方法:
- 生物化学分析以确定ThsA宏域的核酸结合特异性.
- 结晶学以解决ThsA寡合化的结构基础.
- 在基预测和局部定向突变发生,以确定ThsA功能中的关键残留物.
- 对参与核酸生产的ThsB亚家族酶的分析.
主要成果:
- ThsA宏域结合ADP-ribose (ADPR) 和伊米达腺因二核酸 (IAD),但不是2'cADPR或3'cADPR.
- 核酸结合会诱导ThsA宏域的寡合化和TM域的聚合.
- 特定的ThsB亚家族产生ADPR和IAD,其活性位点类似于核酸加工酶.
- 对于SIR2-SLOG和TM-宏ThsA效应因子,已经确定了不同的激活机制.
结论:
- 托雷斯系统在ThsA效应机制中表现出功能多样性.
- TM-宏ThsA效应器利用了一种新的途径,涉及ADPR和IAD结合用于细菌防御.
- 了解这些独特的途径,可以深入了解 prokaryotic 免疫系统的演变.
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