抗 CRISPR 介导免疫抑制的结构与策略。
Structures and Strategies of Anti-CRISPR-Mediated Immune Suppression.
机构信息
Department of Microbiology and Immunology, Montana State University, Bozeman, Montana 59717, USA; email:
Department of Microbiology and Immunology and Quantitative Biosciences Institute, University of California, San Francisco, California 94143, USA.
出版信息
Annu Rev Microbiol. 2020 Sep 8;74:21-37. doi: 10.1146/annurev-micro-020518-120107. Epub 2020 Jun 5.
Abstract
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.
摘要
已经鉴定出 50 多种蛋白质家族可以抑制 CRISPR（成簇规律间隔短回文重复序列）-Cas 介导的适应性免疫系统。在这里，我们分析了现有的抗 CRISPR（Acr）结构，并描述了 CRISPR-Cas 系统的化学计量和酶抑制剂的常见主题和独特机制。化学计量抑制剂通常作为蛋白质结合伙伴或核酸靶标的分子诱饵发挥作用，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。我们综述了 Acrs 结构所揭示的机制见解，讨论了这些策略中的每一种所涉及的权衡，并强调了 Acrs 如何在克服适应性免疫的竞争中被调控和部署。
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