A Protein-Cutting CRISPR Complex Caught in Action
A Protein-Cutting CRISPR Complex Caught in Action
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蛋白质切割 CRISPR 复合物发挥作用
DOI：
10.1089/crispr.2022.29154.aha
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Hatoum-Aslan, Asma
中科院分区：
文献类型：
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作者：
Hatoum-Aslan, Asma
III型CRISPR-Cas系统被认为是六种CRISPR类型中最复杂的，现在随着III-E型的发现，它们也被证明是最通用的。III型系统被归类为I类，使用通常由多个亚基组成的效应复合物对外源RNA发起复杂的多层免疫应答。除了编码效应复合物的核心基因之外，已经发现III型基因座含有编码多种酶（包括核酸酶和蛋白酶）的各种辅助基因。1，2尽管辅助核酸酶在III型免疫应答中的募集和激活机制已经建立，但蛋白酶是否以及如何参与免疫仍然是一个谜。为了解决这个难题，由Ailong Ke（康奈尔大学）和Stan Brouns（德尔夫特理工大学）领导的两个团队共同努力，揭示了与蛋白酶复合的III-E CRISPR-Cas系统在RNA识别时触发蛋白质切割的机制。3，4 III型系统分为六个亚型（A-F），它们具有略微不同的cas基因组成（表1）。其中，III-E型系统是该系列的最新成员。5它们在宏基因组数据集中被生物信息学鉴定为类似于III型系统，但有几个特征使它们与众不同。
Type III CRISPR-Cas systems are reputed to be the most complex of the six CRISPR types, and now with the discovery of Type III-E, they are also proving to be the most versatile. Categorized as Class I, Type III systems launch a sophisticated and multilayered immune response to foreign RNA using effector complexes typically composed of multiple subunits. In addition to the core genes that code for the effector complex, Type III loci have been found to harbor an assortment of accessory genes that encode a variety of enzymes, including nucleases and proteases. 1, 2Although accessory nucleases now have wellestablished mechanisms for recruitment and activation during the Type III immune response, whether and how a protease can become involved in immunity has remained elusive. Solving this puzzle, two teams led by Ailong Ke (Cornell University) and Stan Brouns (Delft University of Technology) combined their efforts to reveal the mechanism by which a Type III-E CRISPR-Cas system in complex with a protease triggers protein cleavage upon RNA recognition. 3, 4 Type III systems are divided into six subtypes (A–F) that have slightly different cas gene compositions (Table 1). Of these, Type III-E systems are among the newest additions to the family. 5 They were bioinformatically identified in metagenomic data sets as resembling Type III systems but have several features that set them apart.