非编码RNA调解了与防御相关的逆转录酶 (DRT) 抗菌体寡合化过渡.
Jie Han1,2,3, Bin Liu1,2, Jingjing Tang4,5
1Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin Medical University Cancer Institute and Hospital, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Institute of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
The EMBO journal
|August 20, 2025
概括
与防御相关的逆转录酶 (DRT) 系统提供 prokaryotic 抗病毒防御. 这项研究揭示了DRT9系统.
科学领域:
- 分子生物学分子生物学
- 微生物学 微生物学
- 结构生物学 结构生物学
背景情况:
- 与防御相关的逆转录酶 (DRT) 系统对于 prokaryotic 对病毒感染的防御至关重要.
- DRT系统的精确分子机制,特别是它们的结构动力学和激活过程,仍然在很大程度上未被描述.
- 了解这些系统对于破译微生物免疫力和开发新型抗病毒策略至关重要.
研究的目的:
- 阐明两个组成部分的DRT9系统抗病毒活性的分子机制和结构基础.
- 描述非编码RNA (ncRNA) 在DRT9系统组装和激活中的作用.
- 为了研究DRT9逆转录酶 (RT) 在基质结合时的结构转换和酶激活.
主要方法:
- 电子显微镜 (cryo-EM) 用于在各种功能状态下确定DRT9的高分辨率结构.
- 生物化学试验分析蛋白质原始DNA合成活性和基质结合.
- 遗传学分析和功能测试以确定关键蛋白质域及其作用.
主要成果:
- DRT9系统包括逆转录酶 (RT) 和非编码RNA (ncRNA),在菌体感染时表现出蛋白质原始DNA合成.
- 冷EM结构显示DRT9 RT与ncRNA形成二元二元体的二元体,在基质结合后转换为二元体的三元体.
- ncRNA促进合作性自我组装,基质结合通过酶激活的"锁开关"机制诱导构造变化.
- 一个独特的N端螺旋延伸被确定为ncRNA稳定和酶活性必不可少,将DRT9与其他RT系统区分开来.
结论:
- 该DRT9系统采用独特的ncRNA介导的寡合化和形态切换机制,用于抗病毒防御.
- 已确定的N端螺旋延伸对DRT9功能至关重要,突出显示了逆转录酶活性的新方面.
- 这项研究扩大了DRT系统已知的功能和机制多样性,为微生物抗病毒策略提供了洞察力.
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