Structures and Strategies of Anti-CRISPR-Mediated Immune Suppression.

Structures and Strategies of Anti-CRISPR-Mediated Immune Suppression.
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DOI:
10.1146/annurev-micro-020518-120107
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发表时间:
2020-09-08
影响因子:
10.5
通讯作者:
Wiedenheft B
Wiedenheft B
中科院分区:
生物学1区
文献类型:
--
作者:
Wiegand T;Karambelkar S;Bondy-Denomy J;Wiedenheft B

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已经鉴定出近50个蛋白家族可以抑制CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-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的共同主题和独特机制。化学计量抑制剂可以立体阻断与DNA的相互作用或阻止招募或激活Cas核酸酶的构象变化,而酶抑制剂则可以共价修饰Cas蛋白或切割CRISPR RNA。在这里,我们讨论与每种策略相关的一些权衡,并强调acr的原子分辨率结构揭示的机制见解。
Nearly fifty 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 sterically block interactions with DNA or prevent conformational changes that recruit or activate Cas nucleases, whereas enzymatic inhibitors covalently modify Cas proteins or cleave the CRISPR RNA. Here, we discuss some of the trade-offs associated with each of these strategies and highlight mechanistic insights revealed by atomic-resolution structures of Acrs.
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影响因子: 64.8
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