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Allosteric activation mechanism of the type VII CRISPR-Cas system 期刊论文

编号：

3C9C077FCFA4255ECDC49C28F0E26B17
作者：

Zhang, Shuqin#^[1,2]Liu, Yingcan^[1];Wu, Wenqi^[1,2,3];Liu, Zhikun^[1];He, Qiuqiu^[1];Wang, Tongyao^[1];Yang, Jie^[1];Yin, Hang^[1,4];Yuan, Zhiyong(袁智勇)^[5]Zhang, Heng*^[1,2,5]
语种：

英文
期刊：

NUCLEIC ACIDS RESEARCH ISSN：0305-1048 2026 年 54 卷 6 期 ; APR 13
收录：
摘要：

Type VII CRISPR-Cas system, evolutionarily associated with type III systems, utilizes a Cascade complex formed by Cas5 and catalytically inactive Cas7 copies for target RNA binding, but instead incorporates a specialized Cas14 ribonuclease for target cleavage. Here, we report a high-quality cryo-EM structure at the target engagement state with a shortened crRNA and elucidate how the recruited Cas14 captures the target RNA and undergoes target-mediated activation. The signature Cas14 is homologous to eukaryotic CPSF73 and prokaryotic RNase J, comprising two conserved subdomains, M beta L and beta-CASP. Different from canonical type III systems, 5 '-end target RNA, rather than 3 '-end, is bent into the positively charged binding channel formed by the two subdomains to access the conserved catalytic pocket on Cas14. Two special structural features, alpha 1 helix from Cas7 and alpha 10 helix from Cas14, promote the bent target RNA docking into the catalytic pocket of Cas14 nuclease in concert. A dual-functional loop, displaced by the entering target RNA, induces a closed-to-open transition between the two subdomains for nuclease activation. More importantly, the flipped dual-functional loop also maintains the stabilization of incoming target RNA. Altogether, our work provides a more comprehensive understanding of type VII system mechanism, laying a mechanistic foundation for RNA-targeting tool development.
推荐引用方式
GB/T 7714：

Zhang Shuqin,Liu Yingcan,Wu Wenqi, et al. Allosteric activation mechanism of the type VII CRISPR-Cas system [J].NUCLEIC ACIDS RESEARCH,2026,54(6).
APA：

Zhang Shuqin,Liu Yingcan,Wu Wenqi,Liu Zhikun,&Zhang Heng.(2026).Allosteric activation mechanism of the type VII CRISPR-Cas system .NUCLEIC ACIDS RESEARCH,54(6).
MLA：

Zhang Shuqin, et al. "Allosteric activation mechanism of the type VII CRISPR-Cas system" .NUCLEIC ACIDS RESEARCH 54,6(2026).
入库时间：

4/30/2026 9:35:04 PM
更新时间：

4/30/2026 9:35:04 PM

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