在细菌中产生STING循环二核酸传感
Benjamin R Morehouse1,2, Apurva A Govande1,2, Adi Millman3
1Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Nature
|September 3, 2020
概括
刺激干扰素基因 (STING) 途径对免疫至关重要,其起源于细菌. 研究人员发现了功能性细菌性STING, 揭示了它对抗病毒和细菌的天生的免疫力.
科学领域:
- 免疫学
- 结构生物学
- 进化生物学
背景情况:
- 干扰素基因刺激器 (STING) 是人类先天免疫系统的关键受体,在感染期间感知循环二核酸.
- 它的独特结构阻碍了对其起源和哺乳动物循环二核酸信号的理解.
研究的目的:
- 研究STING信号的演化起源和功能机制.
- 阐明涉及 prokaryotes 的保存信号通路.
主要方法:
- 细菌STING同类的晶体结构的确定.
- 细菌和甲基动物STING的结构分析.
- 在STING获取过程中重建进化事件.
主要成果:
- 在 prokaryotic 防御岛屿中识别了功能性 STING 同类物,具有保存的激活机制.
- 确定了细菌STING的结构, 揭示了对循环二GMP反应的最小支架.
- 证明了甲状病毒STING如何进化为抗病毒转录调节.
结论:
- 循环GMP-AMP合成酶 (cGAS) -STING通路在 prokaryotes 中保留,以防御细菌菌体.
- 细菌STING利用了一种涉及循环二核酸识别和丝形成的保存机制.
- 甲基动物的刺痛从原生生物进化而来,适应复杂的免疫调节.
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