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-Structure paper
タイトル | An anti-CRISPR protein disables type V Cas12a by acetylation. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 26, Issue 4, Page 308-314, Year 2019 |
掲載日 | 2019年4月1日 |
著者 | Liyong Dong / Xiaoyu Guan / Ningning Li / Fan Zhang / Yuwei Zhu / Kuan Ren / Ling Yu / Fengxia Zhou / Zhifu Han / Ning Gao / Zhiwei Huang / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Struct Mol Biol / PubMed:30936526 |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.052 - 3.6 Å |
構造データ | EMDB-9742, PDB-6iv6: PDB-6iuf: |
化合物 | ChemComp-ACO: ChemComp-GOL: ChemComp-HOH: |
由来 |
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キーワード | IMMUNE SYSTEM / enzyme / IMMUNE SYSTEM/RNA / IMMUNE SYSTEM-RNA complex |