6iv6 | pdb_00006iv6

Cryo-EM structure of AcrVA5-acetylated MbCas12a in complex with crRNA

Loading... Status: waiting for Mol* initialization Structural highlights 6iv6 is a 2 chain structure with sequence from Moraxella bovoculi and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.6Å Ligands: ALY Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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