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Nucleic Acids Res. 2019 Jun 4;47(10):5420-5428. doi: 10.1093/nar/gkz269.

Structural insights into the modulatory role of the accessory protein WYL1 in the Type VI-D CRISPR-Cas system.

Author information

1
Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
2
The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
3
Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.

Abstract

The Type VI-D CRISPR-Cas system employs an RNA-guided RNase Cas13d with minimal targeting constraints to combat viral infections. This CRISPR system contains RspWYL1 as a unique accessory protein that plays a key role in boosting its effector function on target RNAs, but the mechanism behind this RspWYL1-mediated stimulation remains completely unexplored. Through structural and biophysical approaches, we reveal that the full-length RspWYL1 possesses a novel three-domain architecture and preferentially binds ssRNA with high affinity. Specifically, the N-terminus of RspWYL1 harbors a ribbon-helix-helix motif reminiscent of transcriptional regulators; the central WYL domain of RspWYL1 displays a Sm-like β-barrel fold; and the C-terminal domain of RspWYL1 primarily contributes to the dimerization of RspWYL1 and may regulate the RspWYL1 function via a large conformational change. Collectively, this study provides a first glimpse into the complex mechanism behind the RspWYL1-dictated boosting of target ssRNA cleavage in the Type VI-D CRISPR-Cas system.

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