SNAP output for PDB entry 6iv6 [SNAP web server]

PDB-id

6iv6; SNAP-derived features in text and JSON formats; DNAproDB

Class

immune system-RNA

Method

cryo-EM (3.6 Å)

Summary

cryo-EM structure of acrva5-acetylated mbcas12a in complex with crrna

Reference

Dong L, Guan X, Li N, Zhang F, Zhu Y, Ren K, Yu L, Zhou F, Han Z, Gao N, Huang Z (2019): "An anti-CRISPR protein disables type V Cas12a by acetylation." Nat. Struct. Mol. Biol., 26, 308-314. doi: 10.1038/s41594-019-0206-1.

Abstract

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.