Abstract：
Despite a wide presence of type III clustered regularly interspaced short palindromic repeats, CRISPR-associated (CRISPR-Cas) in archaea and bacteria, very few anti-CRISPR (Acr) proteins inhibiting type III immunity have been identified, and even less is known about their inhibition mechanism. Here, we present the discovery of a type III CRISPR-Cas inhibitor, AcrIIIB2, encoded by Sulfolobus virus S. islandicus rod-shaped virus 3 (SIRV3). AcrIIIB2 inhibits type III-B CRISPR-Cas immune response to protospacers encoded in middle/late-expressed viral genes. Investigation of the interactions between S. islandicus type III-B CRISPR-Cas Cmr-α-related proteins and AcrIIIB2 reveals that the Acr does not bind to Csx1 but rather interacts with the Cmr-α effector complex. Furthermore, in vitro assays demonstrate that AcrIIIB2 can block the dissociation of cleaved target RNA from the Cmr-α complex, thereby inhibiting the Cmr-α turnover, thus preventing host cellular dormancy and further viral genome degradation by the type III-B CRISPR-Cas immunity.
摘要：
尽管广泛存在III型成簇的规则间隔的短回文重复序列，古细菌和细菌中的CRISPR相关（CRISPR-Cas），很少有抗CRISPR（Acr）蛋白抑制III型免疫，对它们的抑制机制知之甚少。这里,我们发现了一种III型CRISPR-Cas抑制剂，AcrIIIB2，由Sulfolobus病毒S.islandicus杆状病毒3（SIRV3）编码。AcrIIIB2抑制III-B型CRISPR-Cas对中/晚期表达病毒基因编码的原间隔区的免疫应答。对S.islandicusIII-B型CRISPR-CasCmr-α相关蛋白与AcrIIIB2之间相互作用的研究表明，Acr不与Csx1结合，而是与Cmr-α效应子复合物相互作用。此外，体外实验表明，AcrIIIB2可以阻断裂解的靶RNA与Cmr-α复合物的解离，从而抑制Cmr-α周转，从而通过III-B型CRISPR-Cas免疫阻止宿主细胞休眠和进一步的病毒基因组降解。
