细菌的cGAS类酶合成各种核酸信号
Aaron T Whiteley1,2, James B Eaglesham1,2, Carina C de Oliveira Mann1,2
1Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Nature
|February 22, 2019
概括
研究人员发现了一种新的细菌酶家族,即循环核酸样核酸转移酶 (CD-NTases),可以产生多种循环二核酸和三核酸. 这些分子影响宿主-病原体相互作用和微生物社区动态.
科学领域:
- 微生物学
- 生物化学
- 结构生物学
背景情况:
- 循环二核酸 (CDN) 是关键的细菌第二信使,参与恒温和毒性.
- 细菌CDN可以在感染期间通过模式识别受体触发宿主免疫反应.
研究的目的:
- 系统地选细菌信号核酸.
- 确定参与CDN合成的新型酶.
- 描述新发现的核基转移酶的结构和功能.
主要方法:
- 对细菌信号核酸进行系统的生化选.
- 蛋白质的表达和净化.
- 进行X射线结晶学以确定酶结构.
- 用于分析酶活性和产品形成的生物化学测试.
- 细胞测试以评估宿主受体的激活.
主要成果:
- 发现了cGAS/DncV类核转移酶 (CD-NTases) 的一个大家族.
- CD-NTase 合成各种循环二核酸 (CDN),使用纯氨酸和氨酸核酸.
- 结构分析显示了负责核酸选择的酶活性部位.
- 除了CDN之外,还可以识别循环三核酸产物.
- 证明这些循环分子会激活不同的宿主受体.
结论:
- CD-NTase 是一种具有广泛基质特异性的保护性酶家族.
- 由CD-NTases合成的多种循环核酸产物可以调节宿主-病原体和宿主-微生物群的相互作用.
- 这些发现扩大了我们对细菌信号分子及其对宿主免疫和生态的影响的理解.
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