CRISPR 介导的抗病毒免疫中 CMR 复合物的结构与机制。
Structure and mechanism of the CMR complex for CRISPR-mediated antiviral immunity.
机构信息
Biomedical Sciences Research Complex, University of St Andrews, Fife KY16 9ST, UK.
出版信息
Mol Cell. 2012 Feb 10;45(3):303-13. doi: 10.1016/j.molcel.2011.12.013. Epub 2012 Jan 5.
Abstract
The prokaryotic clusters of regularly interspaced palindromic repeats (CRISPR) system utilizes genomically encoded CRISPR RNA (crRNA), derived from invading viruses and incorporated into ribonucleoprotein complexes with CRISPR-associated (CAS) proteins, to target and degrade viral DNA or RNA on subsequent infection. RNA is targeted by the CMR complex. In Sulfolobus solfataricus, this complex is composed of seven CAS protein subunits (Cmr1-7) and carries a diverse "payload" of targeting crRNA. The crystal structure of Cmr7 and low-resolution structure of the complex are presented. S. solfataricus CMR cleaves RNA targets in an endonucleolytic reaction at UA dinucleotides. This activity is dependent on the 8 nt repeat-derived 5' sequence in the crRNA, but not on the presence of a protospacer-associated motif (PAM) in the target. Both target and guide RNAs can be cleaved, although a single molecule of guide RNA can support the degradation of multiple targets.
摘要
原核生物规律成簇间隔短回文重复序列（CRISPR）系统利用基因组编码的 CRISPR RNA（crRNA），源自入侵病毒，并与 CRISPR 相关（CAS）蛋白整合到核糖核蛋白复合物中，靶向并降解随后感染的病毒 DNA 或 RNA。RNA 由 CMR 复合物靶向。在 Sulfolobus solfataricus 中，该复合物由七个 CAS 蛋白亚基（Cmr1-7）组成，并携带多样化的靶向 crRNA“有效载荷”。介绍了 Cmr7 的晶体结构和复合物的低分辨率结构。S. solfataricus CMR 在 UA 二核苷酸处通过内切核酸酶反应切割 RNA 靶标。该活性依赖于 crRNA 中 8nt 重复衍生的 5'序列，但不依赖于靶标中存在原间隔序列邻近基序（PAM）。靶标和向导 RNA 都可以被切割，尽管单个向导 RNA 分子可以支持多个靶标的降解。
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