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Cas1 Mediates the Interference Stage in a Phage-encoded CRISPR-Cas System

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Journal Nat Chem Biol
Date 2024 Jul 8
PMID 38977786
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Abstract

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems are prokaryotic adaptive immune systems against invading phages and other mobile genetic elements. Notably, some phages, including the Vibrio cholerae-infecting ICP1 (International Center for Diarrheal Disease Research, Bangladesh cholera phage 1), harbor CRISPR-Cas systems to counteract host defenses. Nevertheless, ICP1 Cas8f lacks the helical bundle domain essential for recruitment of helicase-nuclease Cas2/3 during target DNA cleavage and how this system accomplishes the interference stage remains unknown. Here, we found that Cas1, a highly conserved component known to exclusively work in the adaptation stage, also mediates the interference stage through connecting Cas2/3 to the DNA-bound CRISPR-associated complex for antiviral defense (Cascade; CRISPR system yersinia, Csy) of the ICP1 CRISPR-Cas system. A series of structures of Csy, Csy-dsDNA (double-stranded DNA), Cas1-Cas2/3 and Csy-dsDNA-Cas1-Cas2/3 complexes reveal the whole process of Cas1-mediated target DNA cleavage by the ICP1 CRISPR-Cas system. Together, these data support an unprecedented model in which Cas1 mediates the interference stage in a phage-encoded CRISPR-Cas system and the study also sheds light on a unique model of primed adaptation.

References
1.
Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S . CRISPR provides acquired resistance against viruses in prokaryotes. Science. 2007; 315(5819):1709-12. DOI: 10.1126/science.1138140. View

2.
Bolotin A, Quinquis B, Sorokin A, Ehrlich S . Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology (Reading). 2005; 151(Pt 8):2551-2561. DOI: 10.1099/mic.0.28048-0. View

3.
Marraffini L, Sontheimer E . CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA. Science. 2008; 322(5909):1843-5. PMC: 2695655. DOI: 10.1126/science.1165771. View

4.
Makarova K, Wolf Y, Iranzo J, Shmakov S, Alkhnbashi O, Brouns S . Evolutionary classification of CRISPR-Cas systems: a burst of class 2 and derived variants. Nat Rev Microbiol. 2019; 18(2):67-83. PMC: 8905525. DOI: 10.1038/s41579-019-0299-x. View

5.
Koonin E, Makarova K, Zhang F . Diversity, classification and evolution of CRISPR-Cas systems. Curr Opin Microbiol. 2017; 37:67-78. PMC: 5776717. DOI: 10.1016/j.mib.2017.05.008. View