Science：细菌CRISPR适应性防御机制新见解

佰通生物

原文地址连接：Science：细菌CRISPR适应性防御机制新见解   更多精彩新闻请点击：佰通生物

      细菌都会有一种复杂的自我防御机制，近日，刊登在国际著名杂志Science上的两篇研究论文中，来自史丹福大学直线加速国家实验室（SLAC National Accelerator Laboratory）的研究人员通过研究提出了名为CRISPR的细菌适应性防御系统的新见解，CRISPR是有规律间隔的短回文重复序列。
      研究者表示，细菌的这部分免疫系统可以以一种保持记录的角色来发挥作用，其可以帮助细菌注意攻击病毒的身份并且通过将病毒的DNA整合入自身的DNA的方式来保存病毒的信息；CRISPR可以保持此前所遭遇过的所有病毒的信息，并且可以很轻松地使得细菌的免疫系统释放效应物来杀灭再次入侵的外来病毒。
      发表在去年Science上的一篇研究报告中，研究人员不仅揭示了细菌如何击退外来的病毒，而且他们还表示，细菌的这种技术或许可以帮助人类潜在地抵御疾病的感染；当前研究者正在通过利用细菌的CRISPER系统来开发预防和治疗囊性纤维化、血液障碍、HIV的新型策略。文章中研究人员利用X射线技术对一种名为Cascade的CRISPER系统相关复合物进行了研究，在大肠杆菌中，11种蛋白质组合起来同时同RNA一起就可以帮助Cascade来靶向作用入侵的DNA序列，一旦Cascade证实靶向作用的DNA是来自外来入侵者的，一种分析信号就会促使一种名为Cas3的核酸酶去消灭入侵者。
      此前研究中研究者发现Cascade复合物是一种类似于海马状的结构，而在本文研究中研究者表示，我们揭示了这种复合物的各部分是如何装配起来形成完整功能的复合物的，确定大分子的高分辨率结构依然具有较大的挑战性；本文研究揭示了Cascade复合物的RNA向导并不会和病毒的DNA相互扭结形成螺旋，相反它们会形成一种伤口丝带状的结构。
      高分辨率的结构对于进行分子生物机器蓝图的规划非常关键，然而确定复合物的精细结构对于研究其组装的各部分的功能也非常重要，对于开发治疗新型的疗法及治理策略也是不可或缺的。
推荐的原始文献：
[1] Jackson, R. N. et al. "Crystal structure of the CRISPR RNA-guided surveillance complex from Escherichia coli." Science (2014) DOI:10: 10.1126/science.1256328.
[2] Mulepati S, et al. "Crystal structure of a CRISPR RNA-guided surveillance complex bound to a ssDNA target." Science (2014) 345:1479–1484.
推荐的新闻阅读：
Bacteria have a sophisticated means of defending themselves, and they need it: more viruses infect bacteria than any other biological entity.
Two experiments undertaken at the Department of Energy's SLAC National Accelerator Laboratory provide new insight at the heart of bacterial adaptive defenses in a system called CRISPR, short for Clustered Regularly Interspaced Short Palindromic Repeat.
This portion of bacteria's immune system works as a record keeper, taking note of attacking viruses' identities and storing that information by integrating fragments of the virus' DNA into its own DNA. In this way, CRISPRs maintain genetic records of previously encountered viruses, making it easier for the bacteria's immune system to send out complexes that destroy viral invaders by identifying and cutting up the recognized DNA sequences.
The studies published last year in Science not only reveal important information about how bacteria repel attacking viruses, but also could potentially improve the prevention of disease in humans. Researchers are currently studying ways of preventing and treating cystic fibrosis, blood disorders and HIV by harnessing the CRISPR system to replace one version of a gene with another or to add a working copy for a mutated gene.
Scientists studied one particular CRISPR-associated complex called Cascade using bright X-rays at SLAC's Stanford Synchrotron Radiation Lightsource (SSRL), a DOE Office of Science User Facility. In the bacteria Escherichia coli, 11 proteins assemble together with an RNA guide that helps Cascade target invading DNA sequences. Once Cascade confirms that the target DNA is from an invader, a molecular signal recruits a nuclease called Cas3 to finish off the invader by chewing it up......