超分子抗菌体防御复合体的冷EM结构
Brianna Duncan-Lowey1, Nitzan Tal2, Alex G Johnson1
1Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Cell
|February 10, 2023
概括
该RADAR细菌防御系统使用RdrA和RdrB蛋白质将ATP转化为ITP,限制菌体的复制. 这种核酸修饰是雷达的关键.
科学领域:
- 细菌免疫和防御机制
- 结构生物学和冷电子显微镜
- 核酸代谢的分子机制
背景情况:
- 雷达 (DNA相关活动识别) 是一种细菌防御系统.
- 之前人们认为它通过修改信使RNA来防御细菌菌体.
- 详细的分子结构和机制在很大程度上是未知的.
研究的目的:
- 确定雷达防御综合体的冷电子显微镜 (冷EM) 结构.
- 阐明RADAR赋予抗菌素免疫力的分子机制.
- 确定涉及防御的特定核酸修饰.
主要方法:
- 低温电子显微镜 (cryo-EM) 来解析RADAR复合体的高分辨率结构.
- 在体外测试酶活性的生物化学测试.
- 在活体实验中观察菌体感染期间的核酸积累.
主要成果:
- 冷-EM结构显示RdrA是一种HEPTAMERICAAA+ATPase,而RdrB则是一种具有deaminase活性位点的多倍体复合物.
- RdrA和RdrB形成一个大型组件 (最多10MDa),RdrA位于RdrB的活性部位上.
- 在实验室中,RdrB催化了ATP转化为三酸 (ITP),并导致菌体感染期间的ITP积累,从而抑制菌体的复制.
结论:
- 雷达免疫是由ATP单核酸去胺而不是RNA编辑来决定的.
- 这项研究揭示了一种通过核酸修饰机器的超分子组合的新型抗菌素防御机制.
- 这项工作重新定义了RADAR系统在细菌防御中的功能.
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