AcrIF7 (also known as AcrF7) is an anti-CRISPR (Acr) protein that was discovered via the guilt-by association (GBA) approach, which is based on the strong co-occurrence and clustering of acr and anti-CRISPR associated (aca) genes through proximity and homology searches. Functional assays show that AcrIF7 in Pseudomonas aeruginosa prophages strongly inhibits the type I-F CRISPR-Cas system. It has been classified as a broad-range type I-F Acr, as it is able to block the type I-F system of both P. aeruginosa and Pectobacterium atrosepticum. AcrIF7 targets the Cas8f subunit of the Csy complex and may compete for the same binding interface with AcrIF2. Extensive mutagenic analyses revealed that AcrIF7 associated with the highly conserved dsDNA binding site of Cas8f, primarily via electrostatic interactions. 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, and they inhibit a wide range of CRISPR-Cas systems with various inhibition mechanisms. 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.
Comment:AcrIF7 targets the Cas8f-Cas5f tail of the Csy complex to compete with target DNA binding, however this interaction is driven mainly by electrostatic interactions
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