Structural rearrangements allow nucleic acid discrimination by type I-D Cascade

Evan A. Schwartz, Tess M. McBride, Jack P. K. Bravo, Daniel Wrapp, Peter C. Fineran, Robert D. Fagerlund and David W. Taylor ()
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Evan A. Schwartz: University of Texas at Austin
Tess M. McBride: University of Otago
Jack P. K. Bravo: University of Texas at Austin
Daniel Wrapp: University of Texas at Austin
Peter C. Fineran: University of Otago
Robert D. Fagerlund: University of Otago
David W. Taylor: University of Texas at Austin

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-30402-8

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