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Publication Abstract from PubMed

CRISPR-Cas systems are prokaryotic antiviral systems, and phages use anti-CRISPR proteins (Acrs) to inactivate these systems. Here we present structural and functional analyses of AcrIF5, exploring its unique anti-CRISPR mechanism. AcrIF5 shows binding specificity only for the target DNA-bound form of the crRNA-guided surveillance (Csy) complex, but not the apo Csy complex from the type I-F CRISPR-Cas system. We solved the structure of the Csy-dsDNA-AcrIF5 complex, revealing that the conformational changes of the Csy complex caused by dsDNA binding dictate the binding specificity for the Csy-dsDNA complex by AcrIF5. Mechanistically, five AcrIF5 molecules bind one Csy-dsDNA complex, which destabilizes the helical bundle domain of Cas8f, thus preventing subsequent Cas2/3 recruitment. AcrIF5 exists in symbiosis with AcrIF3, which blocks Cas2/3 recruitment. This attack on the recruitment event stands in contrast to the conventional mechanisms of blocking binding of target DNA. Overall, our study reveals an unprecedented mechanism of CRISPR-Cas inhibition by AcrIF5.

AcrIF5 specifically targets DNA-bound CRISPR-Cas surveillance complex for inhibition.,Xie Y, Zhang L, Gao Z, Yin P, Wang H, Li H, Chen Z, Zhang Y, Yang M, Feng Y Nat Chem Biol. 2022 Mar 17. pii: 10.1038/s41589-022-00995-8. doi:, 10.1038/s41589-022-00995-8. PMID:35301482^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.