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

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. Nature Communications. 13, 2829.

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Author
Schwartz, Evan A.; McBride, Tess M.; Bravo, JackISTA ; Wrapp, Daniel; Fineran, Peter C.; Fagerlund, Robert D.; Taylor, David W.
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.
Publishing Year
Date Published
2022-05-20
Journal Title
Nature Communications
Volume
13
Article Number
2829
ISSN
IST-REx-ID

Cite this

Schwartz EA, McBride TM, Bravo JPK, et al. Structural rearrangements allow nucleic acid discrimination by type I-D Cascade. Nature Communications. 2022;13. doi:10.1038/s41467-022-30402-8
Schwartz, E. A., McBride, T. M., Bravo, J. P. K., Wrapp, D., Fineran, P. C., Fagerlund, R. D., & Taylor, D. W. (2022). Structural rearrangements allow nucleic acid discrimination by type I-D Cascade. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-30402-8
Schwartz, Evan A., Tess M. McBride, Jack Peter Kelly Bravo, Daniel Wrapp, Peter C. Fineran, Robert D. Fagerlund, and David W. Taylor. “Structural Rearrangements Allow Nucleic Acid Discrimination by Type I-D Cascade.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-30402-8.
E. A. Schwartz et al., “Structural rearrangements allow nucleic acid discrimination by type I-D Cascade,” Nature Communications, vol. 13. Springer Nature, 2022.
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. Nature Communications. 13, 2829.
Schwartz, Evan A., et al. “Structural Rearrangements Allow Nucleic Acid Discrimination by Type I-D Cascade.” Nature Communications, vol. 13, 2829, Springer Nature, 2022, doi:10.1038/s41467-022-30402-8.
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