Mechanistic insights into the inhibition of the CRISPR-Cas surveillance complex by anti-CRISPR protein AcrIF13

Wang, Hao; Gao, Teng; Zhou, Yu; Ren, Junhui; Guo, Junhua; Zeng, Jianwei; Xiao, Yu; Zhang, Yi; Feng, Yue

doi:10.1016/j.jbc.2022.101636

Cited by 4 publications

(2 citation statements)

References 29 publications

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“…However, the binding site of AcrIF4 on the Csy complex neither conflicts with the hybridization site of the target DNA strand on Cas7f subunits nor shields the PAM recognition region on Cas8f. This is reflected by the fact that Csy-AcrIF4 can still bind dsDNA to form a ternary complex, which is significantly different from the canonical competition approaches utilized by AcrIF1/2/6/7/8/9/10/13/14/24 (11)(12)(13)(17)(18)(19)(20)(21)(22)(23). We found that AcrIF4 shields some residues of the RBC and also disrupts the Cas8f HB part of RBC by preventing rotation of the Cas8f HB.…”

Section: Discussionmentioning

confidence: 72%

Structural and mechanistic insights into inhibition of the type I-F CRISPR-Cas surveillance complex by AcrIF4

Gao

Zhang

et al. 2022

Preprint

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CRISPR-Cas system provides prokaryotes with protection against mobile genetic elements (MGEs) such as phages. In turn, phages deploy anti-CRISPR (Acr) proteins to evade this immunity. AcrIF4, an Acr targeting the type I-F CRISPR-Cas system, has been reported to bind the crRNA-guided surveillance (Csy) complex. However, it remains controversial whether AcrIF4 inhibits target DNA binding to the Csy complex. Here, we present structural and mechanistic studies into AcrIF4, exploring its unique anti-CRISPR mechanism. While the Csy-AcrIF4 complex displays decreased affinity for target DNA, it is still able to bind the DNA. Structural and functional analyses of the Csy-AcrIF4-dsDNA complex revealed that AcrIF4 binding prevents rotation of the helical bundle (HB) of Cas8f induced by dsDNA binding, therefore resulting in failure of Cas2/3 recruitment and DNA cleavage. Overall, our study provides an interesting example of attack on the nuclease recruitment event by an Acr, but not conventional mechanisms of blocking binding of target DNA.

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Section: Discussionmentioning

confidence: 72%

Structural and mechanistic insights into inhibition of the type I-F CRISPR-Cas surveillance complex by AcrIF4

Gao

Zhang

et al. 2022

Preprint

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“…Later, the research group found that there was always an Aca (anti-CRISPR-associated) gene downstream of the anti-CRISPR gene, which inspired the identification of numerous Acr genes (Pawluk et al, 2016;Borges et al, 2017). Subsequent structural and biological characterization found that most Acr proteins directly target Cas protein-crRNA complexes, such as Cascade (Yang et al, 2021;Gao Z. et al, 2022;Wang et al, 2022;Yang et al, 2022), Cas9-sgRNA (Dong et al, 2017;Rauch et al, 2017), Cas12-crRNA (Marino et al, 2018;Zhang et al, 2019), Cas13-crRNA (Lin et al, 2020;Meeske et al, 2020), and play a role by shielding the domain of recognition or binding nucleic acid substrate. A small amount of Acr proteins target apo Cas proteins, for instance, AcrIIC2 targets Cas9 and impedes the loading of sgRNA onto Cas9 proteins and the subsequent assembly of complexes (Zhu et al, 2019).…”

Section: Directly Binding Immune Proteinsmentioning

confidence: 99%

Bacteriophage strategies for overcoming host antiviral immunity

Gao

Feng

2023

Front. Microbiol.

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Phages and their bacterial hosts together constitute a vast and diverse ecosystem. Facing the infection of phages, prokaryotes have evolved a wide range of antiviral mechanisms, and phages in turn have adopted multiple tactics to circumvent or subvert these mechanisms to survive. An in-depth investigation into the interaction between phages and bacteria not only provides new insight into the ancient coevolutionary conflict between them but also produces precision biotechnological tools based on anti-phage systems. Moreover, a more complete understanding of their interaction is also critical for the phage-based antibacterial measures. Compared to the bacterial antiviral mechanisms, studies into counter-defense strategies adopted by phages have been a little slow, but have also achieved important advances in recent years. In this review, we highlight the numerous intracellular immune systems of bacteria as well as the countermeasures employed by phages, with an emphasis on the bacteriophage strategies in response to host antiviral immunity.

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Anti-CRISPR protein AcrIF4 inhibits the type I-F CRISPR-Cas surveillance complex by blocking nuclease recruitment and DNA cleavage

Gao¹,

Zhang²,

Ge³

et al. 2022

Journal of Biological Chemistry

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Mechanistic insights into the inhibition of the CRISPR-Cas surveillance complex by anti-CRISPR protein AcrIF13

Cited by 4 publications

References 29 publications

Structural and mechanistic insights into inhibition of the type I-F CRISPR-Cas surveillance complex by AcrIF4

Structural and mechanistic insights into inhibition of the type I-F CRISPR-Cas surveillance complex by AcrIF4

Bacteriophage strategies for overcoming host antiviral immunity

Anti-CRISPR protein AcrIF4 inhibits the type I-F CRISPR-Cas surveillance complex by blocking nuclease recruitment and DNA cleavage

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