12/9/2023 0 Comments David schwartz evan schwartzCRISPR-Cas complexes are grouped into 2 main classes, 6 types, and >35 sub-types 6, 7. The CRISPR-Cas surveillance complexes use the crRNA as a guide to bind complementary nucleic acid sequences and trigger their degradation 5. Spacers are transcribed and processed into mature CRISPR RNA (crRNA) guides, which assemble with Cas proteins and form CRISPR-Cas surveillance complexes. During CRISPR-Cas immunity, fragments of invading nucleic acids are stored as spacers in the host CRISPR loci 3, 4. CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems provide adaptive immunity by targeting foreign nucleic acids and mobile genetic elements in a sequence-specific manner 2. The evolutionary arms race between prokaryotes and their viral invaders has led bacteria and archaea to evolve defense mechanisms 1. Thus, our data supports a model for the hybrid nature of this complex with features of type III and type I systems. This work elucidates the unique mechanisms used by type I-D Cascade for discrimination of single-stranded and double stranded targets. These structures allow us to model how binding of the anti-CRISPR protein AcrID1 likely blocks target dsDNA binding via competitive inhibition of the DNA substrate engagement with the Cas10d active site. We show that type I-D Cascade is capable of specifically binding ssRNA and reveal how PAM recognition of dsDNA targets initiates long-range structural rearrangements that likely primes Cas10d for Cas3′ binding and subsequent non-target strand DNA cleavage. Here, we present the structures of type I-D Cascade bound to both a double-stranded (ds)DNA and a single-stranded (ss)RNA target at 2.9 and 3.1 Å, respectively. Interestingly, the type I-D interference proteins contain characteristic features of both type I and type III systems. Two of the most prevalent CRISPR-Cas systems include type I and type III. CRISPR-Cas systems are adaptive immune systems that protect prokaryotes from foreign nucleic acids, such as bacteriophages.
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