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cGLRs是先天免疫中的多样化的模式识别受体家族
Yao Li1, Kailey M Slavik2, Hunter C Toyoda2
1Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Parker Institute for Cancer Immunotherapy at Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Cell
|June 28, 2023
概括
循环GMP-AMP合成酶类受体 (cGLR) 是动物广泛存在的模式识别受体. 他们检测DNA和RNA, 合成独特的核酸信号来控制天生的免疫路径.
科学领域:
- 免疫学
- 分子生物学
- 进化生物学
背景情况:
- 循环GMP- AMP合成酶 (cGAS) 是人类先天免疫的关键酶,通过STING检测细胞核DNA引发免疫反应.
- 模式识别受体 (PRR) 对于识别病原体相关的分子模式和启动免疫信号至关重要.
- 了解跨元动物的PRR的多样性和功能对于理解先天免疫的演变至关重要.
研究的目的:
- 发现和描述一种主要的模式识别受体家族,称为cGAS类受体 (cGLRs),跨越metazoan类.
- 阐明cGLRs对核酸配体的反应中的保存信号机制和核酸合成能力.
- 解释cGLRs产生的独特核酸信号如何调节特定的STING依赖性免疫通路.
主要方法:
- 生物信息分析以识别多种类型的甲基动物中的3000个cGLR.
- 预先对150个动物cGLR进行生物化学查,以评估连体特异性和信号活性.
- 在珊瑚和模型中进行结构生物学和体内分析,以确定cGLR功能的分子机制.
主要成果:
- 确定cGAS类受体 (cGLRs) 作为几乎所有甲状动物群中的广泛的先天免疫受体家族.
- 在cGLRs对dSDNA和dSRNA配体的反应中证明了保存的信号机制.
- 发现cGLR合成各种核酸信号异构体,包括cGAMP,c-UMP-AMP和c-di-AMP,以控制不同的信号通路.
结论:
- cGLRs代表动物先天免疫中主要的,在进化过程中保存的模式识别受体家族.
- 通过cGLRs合成不同的核酸信号,可以调节离散的cGLR-STING信号通路.
- 这项研究确立了动物免疫中核酸信号的基本分子规则,扩大了我们对先天免疫多样性的理解.
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