对细菌STING的调节,连接体识别和寡合化的结构洞察
Mei-Hui Hou1, Yu-Chuan Wang1, Chia-Shin Yang1
1Genomics BioSci. & Tech. Co. Ltd., New Taipei, 221411, Taiwan.
Nature communications
|December 21, 2023
概括
细菌刺激干扰素基因 (STING) 结构揭示了调节机制. 晶体结构显示了细菌STING如何控制循环二核酸结合和信号传递,为其演变和功能提供了洞察力.
科学领域:
- 微生物学 微生物学
- 结构生物学 结构生物学
- 免疫学 免疫学 免疫学
背景情况:
- 循环GMP-AMP合成酶 (cGAS) /刺激干扰素基因 (STING) 途径对于动物的抗病毒防御至关重要.
- 甲动物STING的调节已得到充分研究,但细菌STING的调节在很大程度上是未知的.
- 了解细菌性STING是解读 prokaryotes 的先天免疫反应的关键.
研究的目的:
- 阐明细菌STING调节的结构基础.
- 研究细菌中循环二核酸结合和信号传递的机制.
- 探索细菌STING的进化适应,特别是在极端环境中.
主要方法:
- 用X射线晶体学来确定细菌STING的结构.
- 生物化学试验用于研究带结合和寡合化.
- 不同细菌STING变体的结构比较分析.
主要成果:
- 确定了细菌STING的无活性,反平行二维形式的晶体结构.
- 识别了非活跃状态和活跃状态之间的构造过渡,作为开关.
- 揭示了极端友细菌STING中的插入序列,形成一个延伸的盖子来调节抗菌素活性.
- 观察到循环二-AMP以独特的三角形状结合,导致螺旋原纤维和更高阶纤维.
结论:
- 细菌STING利用结构机制,包括形状变化和调节盖,来控制信号传输.
- 结合体识别和寡合化的差异表明细菌STINGs的功能角色和进化路径各不相同.
- 基于这些发现,已经提出了细菌STING结构功能演化的模型.
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