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菌体抗CBASS蛋白同时隔离循环三核酸和二核酸
Xueli Cao1,2, Yu Xiao3,2, Erin Huiting4,2
1Beijing Advanced Innovation Center for Soft Matter Science and Engineering, State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
bioRxiv : the preprint server for biology
|July 3, 2023
概括
菌体蛋白Acb2作为循环GMP-AMP合成酶 (cGAS) 基础免疫的宽谱抑制剂. 它隔离各种循环核酸信号,保护菌体免受细菌循环寡核酸基抗体信号传递 (CBASS) 系统的影响.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
背景情况:
- 基于循环寡核酸的抗菌体信号传递 (CBASS) 是对菌体的关键细菌防御.
- 菌体对抗CBASS (Acb) 蛋白进行编码,以抵消这些系统.
- Acb2是最近发现的一种菌体抗CBASS蛋白,已知能结合循环二核酸.
研究的目的:
- 研究菌体抗CBASS蛋白Acb2.2.的结合能力和抑制机制.
- 为了确定Acb2是否可以中和循环二核酸以外的其他循环寡核酸信号.
- 阐明Acb2对CBASS系统的宽频活动的结构基础.
主要方法:
- 试验室结合试验评估Acb2对各种循环核酸的亲和力.
- 人类细胞中cGAMP介导的STING激活的抑制试验.
- 进行X射线晶体学以确定与循环核酸结合的Acb2的结构.
- 在体内菌体与宿主相互作用测试以评估Acb2对CBASS的保护作用.
主要成果:
- Acb2 结合并隔离广泛的CBASS和cGAS产生的循环二核酸.
- Acb2对CBASS循环三核酸 (cA3和cAAG) 具有高亲和度的结合.
- 结构分析显示,Acb2六合体内有两个不同的结合口袋,允许循环三核酸和循环二核酸同时结合.
- Acb2有效地抑制cGAMP介导的STING活性和cA3介导的内核酶激活.
- 在体内,Acb2可以保护菌体免受III-C型CBASS系统的侵害.
结论:
- Acb2通过隔离各种循环寡核酸信号,作为基于cGAS的免疫力的强大,广泛的抑制剂.
- Acb2的双口袋结构使多个信号分子的同时中和成为可能,突出了先进的菌体反防御策略.
- 在了解和潜在地操纵细菌抗菌素免疫力方面,Acb2 是一个重要的目标.
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