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Structural basis for inhibition of an archaeal CRISPR–Cas type I-D large subunit by an anti-CRISPR protein
Nature Communications ( IF 14.7 ) Pub Date : 2020-11-25 , DOI: 10.1038/s41467-020-19847-x
M Cemre Manav 1, 2 , Lan B Van 1 , Jinzhong Lin 3 , Anders Fuglsang 3 , Xu Peng 3 , Ditlev E Brodersen 1
Affiliation  

A hallmark of type I CRISPR–Cas systems is the presence of Cas3, which contains both the nuclease and helicase activities required for DNA cleavage during interference. In subtype I-D systems, however, the histidine-aspartate (HD) nuclease domain is encoded as part of a Cas10-like large effector complex subunit and the helicase activity in a separate Cas3’ subunit, but the functional and mechanistic consequences of this organisation are not currently understood. Here we show that the Sulfolobus islandicus type I-D Cas10d large subunit exhibits an unusual domain architecture consisting of a Cas3-like HD nuclease domain fused to a degenerate polymerase fold and a C-terminal domain structurally similar to Cas11. Crystal structures of Cas10d both in isolation and bound to S. islandicus rod-shaped virus 3 AcrID1 reveal that the anti-CRISPR protein sequesters the large subunit in a non-functional state unable to form a cleavage-competent effector complex. The architecture of Cas10d suggests that the type I-D effector complex is similar to those found in type III CRISPR–Cas systems and that this feature is specifically exploited by phages for anti-CRISPR defence.



中文翻译:

抗 CRISPR 蛋白抑制古细菌 CRISPR-Cas ID 型大亚基的结构基础

I 型 CRISPR-Cas 系统的一个标志是 Cas3 的存在,它包含干扰期间 DNA 切割所需的核酸酶和解旋酶活性。然而,在亚型 ID 系统中,组氨酸-天冬氨酸 (HD) 核酸酶结构域被编码为类似 Cas10 的大效应复合物亚基的一部分,而解旋酶活性则编码为单独的 Cas3' 亚基,但该组织的功能和机制结果是目前不理解。在这里,我们展示了岛硫化叶菌ID 型 Cas10d 大亚基表现出一种不寻常的结构域结构,由与简并聚合酶折叠融合的 Cas3 样 HD 核酸酶结构域和结构类似于 Cas11 的 C 端结构域组成。分离的 Cas10d 和与S. islandicus杆状病毒 3 AcrID1 结合的 Cas10d 晶体结构表明,抗 CRISPR 蛋白以非功能状态隔离大亚基,无法形成具有裂解能力的效应复合物。Cas10d 的结构表明 ID 型效应复合物与 III 型 CRISPR-Cas 系统中发现的效应复合物相似,并且噬菌体专门利用该功能进行抗 CRISPR 防御。

更新日期:2020-11-26
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