%0 Journal Article
%T Molecular basis for inhibition of type III-B CRISPR-Cas by an archaeal viral anti-CRISPR protein.
%A Lin J
%A Alfastsen L
%A Bhoobalan-Chitty Y
%A Peng X
%J Cell Host Microbe
%V 31
%N 11
%D 2023 11 8
%M 37909049
%F 31.316
%R 10.1016/j.chom.2023.10.003
%X 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.