Structural highlights
Publication Abstract from PubMed
Phages use anti-CRISPR proteins to deactivate the CRISPR-Cas system. The mechanisms for the inhibition of type I and type II systems by anti-CRISPRs have been elucidated. However, it has remained unknown how the type V CRISPR-Cas12a (Cpf1) system is inhibited by anti-CRISPRs. Here we identify the anti-CRISPR protein AcrVA5 and report the mechanisms by which it inhibits CRISPR-Cas12a. Our structural and biochemical data show that AcrVA5 functions as an acetyltransferase to modify Moraxella bovoculi (Mb) Cas12a at Lys635, a residue that is required for recognition of the protospacer-adjacent motif. The AcrVA5-mediated modification of MbCas12a results in complete loss of double-stranded DNA (dsDNA)-cleavage activity. In contrast, the Lys635Arg mutation renders MbCas12a completely insensitive to inhibition by AcrVA5. A cryo-EM structure of the AcrVA5-acetylated MbCas12a reveals that Lys635 acetylation provides sufficient steric hindrance to prevent dsDNA substrates from binding to the Cas protein. Our study reveals an unprecedented mechanism of CRISPR-Cas inhibition and suggests an evolutionary arms race between phages and bacteria.
An anti-CRISPR protein disables type V Cas12a by acetylation.,Dong L, Guan X, Li N, Zhang F, Zhu Y, Ren K, Yu L, Zhou F, Han Z, Gao N, Huang Z Nat Struct Mol Biol. 2019 Apr;26(4):308-314. doi: 10.1038/s41594-019-0206-1. Epub, 2019 Apr 1. PMID:30936526[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dong L, Guan X, Li N, Zhang F, Zhu Y, Ren K, Yu L, Zhou F, Han Z, Gao N, Huang Z. An anti-CRISPR protein disables type V Cas12a by acetylation. Nat Struct Mol Biol. 2019 Apr;26(4):308-314. doi: 10.1038/s41594-019-0206-1. Epub, 2019 Apr 1. PMID:30936526 doi:http://dx.doi.org/10.1038/s41594-019-0206-1
