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Structure of Csy-AcrIF24-dsDNAStructure of Csy-AcrIF24-dsDNA
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 adaptive immune systems and phages use anti-CRISPR proteins (Acrs) to counteract these systems. Here, we report the structures of AcrIF24 and its complex with the crRNA-guided surveillance (Csy) complex. The HTH motif of AcrIF24 can bind the Acr promoter region and repress its transcription, suggesting its role as an Aca gene in self-regulation. AcrIF24 forms a homodimer and further induces dimerization of the Csy complex. Apart from blocking the hybridization of target DNA to the crRNA, AcrIF24 also induces the binding of non-sequence-specific dsDNA to the Csy complex, similar to AcrIF9, although this binding seems to play a minor role in AcrIF24 inhibitory capacity. Further structural and biochemical studies of the Csy-AcrIF24-dsDNA complexes and of AcrIF24 mutants reveal that the HTH motif of AcrIF24 and the PAM recognition loop of the Csy complex are structural elements essential for this non-specific dsDNA binding. Moreover, AcrIF24 and AcrIF9 display distinct characteristics in inducing non-specific DNA binding. Together, our findings highlight a multifunctional Acr and suggest potential wide distribution of Acr-induced non-specific DNA binding. Insights into the inhibition of type I-F CRISPR-Cas system by a multifunctional anti-CRISPR protein AcrIF24.,Yang L, Zhang L, Yin P, Ding H, Xiao Y, Zeng J, Wang W, Zhou H, Wang Q, Zhang Y, Chen Z, Yang M, Feng Y Nat Commun. 2022 Apr 11;13(1):1931. doi: 10.1038/s41467-022-29581-1. PMID:35411005[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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