STING是循环二-GMP的直接天生的免疫传感器
Dara L Burdette1, Kathryn M Monroe, Katia Sotelo-Troha
1Department of Molecular & Cell Biology, University of California, Berkeley, California 94720, USA.
Nature
|September 28, 2011
概括
刺激IFN基因 (STING) 蛋白直接感知循环二核酸,关键的细菌信号分子. 这一发现揭示了刺痛.
科学领域:
- 这是天生的免疫力.
- 分子免疫学分子免疫学
- 信号传导是指信号的传导方式.
背景情况:
- 天生的免疫系统使用生殖系编码的受体来检测保存的微生物分子,触发细胞因子的产生,如I型干扰素 (IFN),对病原体的消除至关重要.
- 细胞核DNA检测通过TANK结合激酶1 (TBK1) 和IFN调节因子3 (IRF3) 诱导IFN的产生.
- STING (IFN基因刺激器) 作为信号适配器,将细胞质DNA检测与TBK1-IRF3通路联系起来;循环二核酸也会诱导依赖STING的IFN反应,但它们的传感器是未知的.
研究的目的:
- 为了识别周期性二核酸的哺乳动物传感器.
- 阐明在先天免疫反应中循环二核酸识别的机制.
- 在循环二核酸的背景下,研究STING在信号适配器之外的作用.
主要方法:
- 使用放射性标记的周期性迪加尼酸单酸盐 (c-di-GMP) 进行结合性测定,以评估STING相互作用.
- 竞争测试使用各种核酸和核酸来确定结合特异性.
- STING的突变发生,以识别影响循环二核酸反应的突变,独立于DNA反应.
主要成果:
- STING直接与循环二核酸结合,特别是c-di-GMP.
- 未标记的循环二核酸,但不是其他核酸或核酸,在STING结合中竞争.
- 鉴定了STING中的突变,这些突变选择性地损害了对循环二核酸的反应,同时保持了对DNA的反应.
结论:
- STING作为循环二核酸的直接先天性免疫传感器,除了作为细胞核DNA的信号适配器之外,还起到作用.
- 这一发现为细菌衍生的循环二核酸如何被宿主天生的免疫系统感知提供了机械的洞察力.
- 了解STING作为传感器和适配器的双重作用对开发循环二核酸作为疫苗辅助剂和免疫疗法药物有影响.
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