6IV6
Cryo-EM structure of AcrVA5-acetylated MbCas12a in complex with crRNA
Summary for 6IV6
| Entry DOI | 10.2210/pdb6iv6/pdb |
| EMDB information | 9742 |
| Descriptor | nuclease, RNA (59-MER) (2 entities in total) |
| Functional Keywords | enzyme, immune system, immune system-rna complex, immune system/rna |
| Biological source | Moraxella bovoculi More |
| Total number of polymer chains | 2 |
| Total formula weight | 163927.29 |
| Authors | |
| Primary citation | 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., 26:308-314, 2019 Cited by PubMed 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. PubMed: 30936526DOI: 10.1038/s41594-019-0206-1 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.6 Å) |
Structure validation
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