SNAP output for PDB entry 7sba [SNAP web server]

PDB-id

7sba; SNAP-derived features in text and JSON formats; DNAproDB

Class

DNA binding protein-DNA-RNA

Method

cryo-EM (2.9 Å)

Summary

Structure of type i-d cascade bound to a dsDNA target

Reference

Schwartz EA, McBride TM, Bravo JPK, Wrapp D, Fineran PC, Fagerlund RD, Taylor DW (2022): "Structural rearrangements allow nucleic acid discrimination by type I-D Cascade." Nat Commun, 13, 2829. doi: 10.1038/s41467-022-30402-8.

Abstract

CRISPR-Cas systems are adaptive immune systems that protect prokaryotes from foreign nucleic acids, such as bacteriophages. Two of the most prevalent CRISPR-Cas systems include type I and type III. Interestingly, the type I-D interference proteins contain characteristic features of both type I and type III systems. 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. 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. 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. This work elucidates the unique mechanisms used by type I-D Cascade for discrimination of single-stranded and double stranded targets. Thus, our data supports a model for the hybrid nature of this complex with features of type III and type I systems.