期刊
SCIENCE
卷 369, 期 6499, 页码 54-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abb6151
关键词
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资金
- National Institutes of Health Director's Pioneer Award [1DPIGM128184-01]
- Geoffrey Beene Cancer Research Center
- Memorial Sloan-Kettering Cancer Center Core Grant [P30CAO08748]
- NIH [GM129430]
The CRISPR RNA (crRNA)-guided nuclease Cas13 recognizes complementary viral transcripts to trigger the degradation of both host and viral RNA during the type VI CRISPR-Cas antiviral response. However, how viruses can counteract this immunity is not known. We describe a listeriaphage (phi LS46) encoding an anti-CRISPR protein (AcrVIA1) that inactivates the type VI-A CRISPR system of Listeria seeligeri. Using genetics, biochemistry, and structural biology, we found that AcrVIA1 interacts with the guide-exposed face of Cas13a, preventing access to the target RNA and the conformational changes required for nuclease activation. Unlike inhibitors of DNA-cleaving Cas nucleases, which cause limited immunosuppression and require multiple infections to bypass CRISPR defenses, a single dose of AcrVIA1 delivered by an individual virion completely dismantles type VI-A CRISPR-mediated immunity.
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