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结构揭示了拦截CRISPRRNA指导监控复合体的病毒抑制机制

Saikat Chowdhury¹, Joshua Carter², MaryClare F Rollins²

¹Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA.

|March 25, 2017

概括

Prokaryotes 使用 CRISPR 适应性免疫力对抗病毒. 病毒进化了抗CRISPR (Acr) 蛋白质以阻止这种防御, 揭示了结构层面的分子军备竞赛.

科学领域:

微生物学
分子生物学
结构生物学

背景情况:

病毒和宿主之间的遗传冲突推动了进化创新.
Prokaryotes 使用 CRISPR-Cas 适应性免疫系统来防御病毒感染.
病毒已经开发出反CRISPR (Acr) 蛋白来抵消宿主CRISPR的防御.

研究的目的:

阐明 Pseudomonas aeruginosa 类型 I-F CRISPR-Cas 免疫系统的抗CRISPR蛋白中介抑制的结构基础.
了解Acr蛋白抑制CRISPR介导的DNA向的分子机制.

主要方法:

使用冷电子显微镜 (cryo-EM) 来确定与AcrF1和AcrF2结合的Csy复合物的结构.
用结构引导的突变发生来验证观察到的相互作用的功能意义.

主要成果:

使用AcrF1和AcrF2的Csy复合体的冷EM结构在3. 4 Å分辨率下确定.
结构显示Acr蛋白与参与crRNA指导监测复合物的DNA识别中的关键残留物结合.
突变分析证实,Acr结合会破坏免疫系统功能的重要相互作用.

结论:

这项研究提供了CRISPR-Cas免疫和病毒反防御机制之间的分子相互作用的结构快照.
Acr蛋白通过直接干扰Csy复合体的DNA结合和监控能力而起作用.
这些发现揭示了 prokaryotic 免疫系统和病毒对手之间的共同进化军备竞赛.

关键词:

美国关于CRISPR的研究在CRISPR-Cas中时间美国抗CRISPR药物一个 crRNA 化电磁场冷电子显微镜类型 I-F

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