CRISPR interference: a structural perspective.
CRISPR interference: a structural perspective.
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DOI：
10.1042/bj20130316
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发表时间：
2013-07-15
期刊：
影响因子：
--
通讯作者：
White MF
中科院分区：
文献类型：
--
作者：
Reeks J;Naismith JH;White MF
CRISPR(有规则间隔的回文重复序列簇)是原核生物的适应性防御系统，提供对病毒等可移动遗传元件的免疫力。基因组编码的crRNA(CRISPR RNA)被Cas(CRISPR相关)蛋白质用来靶向并随后以序列依赖的方式降解入侵实体的核酸。这一过程被称为“干扰”。在本综述中，我们介绍了CRISPR/Cas系统结构生物学的最新进展，重点介绍了催化crRNA生物发生和干扰的Cas蛋白和复合体。结构研究有助于阐明关键机制，包括Cas6和Cas5蛋白对crRNA的识别和切割，其中底物识别和催化水平上的显著差异已变得明显。RAMP结构域存在于Cas5、Cas6、Cas7和Cmr3蛋白家族中，类RAMP结构域存在于Cas2和Cas10中。结构分析还揭示了I型和III型干扰复合体的小亚基之间的进化联系。未来对干扰络合物及其组成成分的研究将改变我们对该系统的理解。
CRISPR (cluster of regularly interspaced palindromic repeats) is a prokaryotic adaptive defence system, providing immunity against mobile genetic elements such as viruses. Genomically encoded crRNA (CRISPR RNA) is used by Cas (CRISPR-associated) proteins to target and subsequently degrade nucleic acids of invading entities in a sequence-dependent manner. The process is known as ‘interference’. In the present review we cover recent progress on the structural biology of the CRISPR/Cas system, focusing on the Cas proteins and complexes that catalyse crRNA biogenesis and interference. Structural studies have helped in the elucidation of key mechanisms, including the recognition and cleavage of crRNA by the Cas6 and Cas5 proteins, where remarkable diversity at the level of both substrate recognition and catalysis has become apparent. The RNA-binding RAMP (repeat-associated mysterious protein) domain is present in the Cas5, Cas6, Cas7 and Cmr3 protein families and RAMP-like domains are found in Cas2 and Cas10. Structural analysis has also revealed an evolutionary link between the small subunits of the type I and type III-B interference complexes. Future studies of the interference complexes and their constituent components will transform our understanding of the system.