核酸介导短质核细胞阿尔戈诺特免疫系统的激活
Jithesh Kottur1, Radhika Malik1, Aneel K Aggarwal1
1Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
bioRxiv : the preprint server for biology
|September 25, 2023
概括
细菌使用SPARTA系统来防御入侵的DNA. 结构研究揭示了SPARTA如何激活来降解DNA并阻止感染.
科学领域:
- 细菌学 细菌学是一门学科.
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 细菌拥有多样化的免疫系统来对抗外来DNA.
- 像SPARTA这样的短 prokaryotic Argonaute (pAgo) 系统对于细菌防御至关重要.
- 在激活时,SPARTA利用其TIR域进行NAD (P) +水解.
研究的目的:
- 通过侵入DNA来阐明SPARTA激活的分子机制.
- 在核酸结合后,可视化SPARTA的结构变化.
- 了解SPARTA的活跃组合和功能的基础.
主要方法:
- 没有核酸的SPARTA异构体的X射线晶体学.
- 结晶电子显微镜 (cryo-EM) 的SPARTA寡合体结合指导RNA/目标ssDNA.
- 对阿波州和全斯巴达州的比较结构分析.
主要成果:
- 斯巴达异构体的晶体结构揭示了详细的域架构.
- 化-EM结构显示,SPARTA形成了一个活跃的四重体寡合体.
- 结构比较确定了关键域重新配置,使核酸结合和激活成为可能.
- 寡合化导致对催化而言平行TIR域的安排.
结论:
- 在核酸结合后,SPARTA经历了显著的形状变化.
- 这些变化缓解了自身抑制,促进了寡合化,并激活了TIR域.
- 这些结构洞察力解释了SPARTA在DNA降解和细菌防御中的作用.
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