6IUF

Crystal structure of Anti-CRISPR protein AcrVA5

Summary for 6IUF

• Entry DOI: 10.2210/pdb6iuf/pdb
• Descriptor: protein-a, ACETYL COENZYME *A, GLYCEROL, ... (4 entities in total)
• Functional Keywords: enzyme, immune system
• Biological source: Moraxella bovoculi
• Total number of polymer chains: 2
• Total formula weight: 23571.48

Authors

Dong, L.,Guan, X.,Zhu, Y.,Huang, Z. (deposition date: 2018-11-28, release date: 2019-04-10, Last modification date: 2024-03-27)

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

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: 30936526
DOI: 10.1038/s41594-019-0206-1

Experimental method

X-RAY DIFFRACTION (2.052 Å)