7eqg
Structure of Csy-AcrIF5Structure of Csy-AcrIF5
Structural highlights
FunctionCSY2_PSEAB CRISPR (clustered regularly interspaced short palindromic repeat) is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA). Cas3 and Cascade participate in CRISPR interference, the third stage of CRISPR immunity (Potential). Absolutely required for crRNA production or stability. The Csy ribonucleoprotein complex binds target ssDNA with high affinity but target dsDNA with much lower affinity.[1] [2] Publication Abstract from PubMedCRISPR-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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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