Structural basis for inhibition of an archaeal CRISPR-Cas type I-D large subunit by an anti-CRISPR protein.
Structural basis for inhibition of an archaeal CRISPR-Cas type I-D large subunit by an anti-CRISPR protein.
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DOI：
10.1038/s41467-020-19847-x
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发表时间：
2020-11-25
影响因子：
16.6
通讯作者：
Brodersen DE
中科院分区：
文献类型：
--
作者：
Manav MC;Van LB;Lin J;Fuglsang A;Peng X;Brodersen DE
I型CRISPR-Cas系统的标志是Cas 3的存在，其含有干扰期间DNA切割所需的核酸酶和解旋酶活性。然而，在亚型I-D系统中，组氨酸-天冬氨酸（HD）核酸酶结构域被编码为Cas 10样大效应复合物亚基的一部分，并且解旋酶活性在单独的Cas 3 '亚基中，但是这种组织的功能和机制后果目前尚不清楚。在这里，我们表明，硫化叶菌islandicus型I-D Cas 10 d大亚基表现出一种不寻常的结构域的架构组成的Cas 3样HD核酸酶结构域融合到一个简并的聚合酶折叠和一个C-末端结构域结构类似于Cas 11。Cas 10 d在分离和结合到S.对islandicus杆状病毒3 AcrID 1的研究表明，抗CRISPR蛋白将大亚基隔离在非功能状态，不能形成有切割能力的效应复合物。Cas 10 d的结构表明，I-D型效应子复合物与III型CRISPR-Cas系统中发现的那些类似，并且这种特征特别被CRISPR用于抗CRISPR防御。在I-D型CRISPR-Cas系统中，核酸酶和解旋酶活性由单独的亚基进行。冰岛硫化叶菌I-D型大亚基Cas 10 d的晶体结构包含一个核酸酶结构域，揭示了不寻常的结构。Cas 10 d与抗CRISPR蛋白AcrID 1复合的结构表明后者将Cas 10 d隔离在非功能状态。
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. In type I-D CRISPR–Cas systems, the nuclease and helicase activities are carried out by separate subunits. The crystal structure of Sulfolobus islandicus type I-D large subunit Cas10d, containing a nuclease domain, reveals unusual architecture. The structure of Cas10d in complex with anti-CRISPR protein AcrID1 suggests that the latter sequesters Cas10d in a nonfunctional state.
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影响因子：
16
作者：
Jia, Ning;Mo, Charlie Y.;Patel, Dinshaw J.
通讯作者：
Patel, Dinshaw J.
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
11.4
作者：
Beloglazova, Natalia;Petit, Pierre;Yakunin, Alexander F.
通讯作者：
Yakunin, Alexander F.
影响因子：
64.5
作者：
Bhoobalan-Chitty, Yuvaraj;Johansen, Thomas Baek;Peng, Xu
通讯作者：
Peng, Xu
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH