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Anti-CRISPR type I subtype D1 (AcrID1) AcrID1 is the first example of anti-CRISPR (Acr) protein found in the archaeal viral domain and the first against the CRISPR-Cas type I-D system discovered via functional assays. AcrID1 inhibits the type I-D system by interacting directly with the Cas10d protein, which is required for the interference stage. AcrID1 belongs to a conserved family of compact, dimeric alpha/beta-sandwich proteins characterized by extreme pH and temperature stability and a tendency to form protein fibers. The type I-D Csy complex is a CRISPR RNA (crRNA)-guided surveillance effector complex that includes a type I signature variant of helicase protein, Cas3, and a type III Cas10-like large subunit, Cas10d, in addition to Csc1 (Cas5) and the backbone protein Csc2 (Cas7). The Cas10d protein is predicted to function as the large subunit of the effector complex and the target-cleaving nuclease, but not as part of a signal transduction pathway as shown for the type III systems. 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.
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