Annual Review of Microbiology ( IF 10.5 ) Pub Date : 2020-09-09 , DOI: 10.1146/annurev-micro-020518-120107 Tanner Wiegand 1 , Shweta Karambelkar 2 , Joseph Bondy-Denomy 2, 3 , Blake Wiedenheft 1
More than 50 protein families have been identified that inhibit CRISPR (clustered regularly interspaced short palindromic repeats)-Cas-mediated adaptive immune systems. Here, we analyze the available anti-CRISPR (Acr) structures and describe common themes and unique mechanisms of stoichiometric and enzymatic suppressors of CRISPR-Cas. Stoichiometric inhibitors often function as molecular decoys of protein-binding partners or nucleic acid targets, while enzymatic suppressors covalently modify Cas ribonucleoprotein complexes or degrade immune signaling molecules. We review mechanistic insights that have been revealed by structures of Acrs, discuss some of the trade-offs associated with each of these strategies, and highlight how Acrs are regulated and deployed in the race to overcome adaptive immunity.
中文翻译:
抗CRISPR介导的免疫抑制的结构和策略。
已经鉴定出50多个蛋白家族可抑制CRISPR(聚簇的规则间隔的短回文重复序列)-Cas介导的适应性免疫系统。在这里,我们分析了可用的抗CRISPR(Acr)结构,并描述了CRISPR-Cas的化学计量和酶抑制剂的共同主题和独特机制。化学计量抑制剂通常充当蛋白质结合伴侣或核酸靶标的分子诱饵,而酶抑制剂则共价修饰Cas核糖核蛋白复合物或降解免疫信号分子。我们回顾了Acrs结构所揭示的机械洞察力,讨论了与每种策略相关的一些取舍,并重点介绍了如何在竞赛中调节和部署Acrs以克服适应性免疫。