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Anti-CRISPR type I subtype F4 AcrIF4 is a phage anti-CRISPR (Acr) protein that has been shown to associate with the type I-F Cascade surveillance complex (type I-F Csy complex) to inhibit DNA binding. AcrIF4 binds the Csy complex with affinities that are orders of magnitude weaker than Acr proteins like AcrIF1 and AcrIF2. The type I-F Csy complex is a crRNA-guided surveillance complex composed of a crRNA and nine Cas proteins (one Cas8f, one Cas5f, one Cas6f, and six Cas7f), which recruits a nuclease-helicase protein Cas3 for target degradation. CRISPR-Cas immune systems are used by certain prokaryotes and archaea to resist the invasion of foreign nucleic acids such as phages or plasmids. Anti-CRISPRs are small proteins which are the natural inhibitors for CRISPR-Cas systems; encoded on bacterial and archaeal viruses, they allow the virus to evade host CRISPR-Cas systems. The CRISPR-Cas-mediated adaptive immune response can be divided into three steps, including the acquisition of spacer derived from invading nucleic acids, crRNA processing, and target degradation. Theoretically, Acr proteins could suppress any step to disrupt the CRISPR-Cas system. Acr proteins are diverse with no common sequence or structural motif, which inhibit a wide range of CRISPR-Cas systems using various inhibition mechanisms. Weak and strong Acr-phages often cooperate to overcome CRISPR resistance, with a first phage blocking the host CRISPR-Cas immune system to allow a second Acr-phage to successfully replicate which leads to epidemiological tipping points. CRISPR-Cas systems are divided into two classes (1 and 2) and six types (class 1: types I, III and IV; class 2: types II, V and VI). Class 1 systems utilize RNA-guided complexes consisting of multiple Cas proteins as the effector proteins to recognize and cleave target DNA. Type I CRISPR-Cas systems are the most widespread in nature, and the Cas protein composition of the employed CRISPR ribonucleoprotein (crRNP) complexes differs between seven subtypes (A to F, U). Acr families are named for their type and subtype which are numbered sequentially as they are discovered. |
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