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现在位置:首页 > 科研进展 > 最新重要论文(影响因子PNAS及以上)
Phage AcrIIA2 DNA Mimicry: Structural Basis of the CRISPR and Anti-CRISPR Arms Race, MOL CELL, 31 Dec 2018
2018-12-31 | 【     】【打印】【关闭

Molecular Cell, 31 December, 2018, DOI: https://doi.org/10.1016/j.molcel.2018.11.011

Phage AcrIIA2 DNA Mimicry: Structural Basis of the CRISPR and Anti-CRISPR Arms Race

Liang Liu, Maolu Yin, Min Wang, Yanli Wang

Summary

CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) systems provide prokaryotic cells with adaptive immunity against invading bacteriophages. Bacteriophages counteract bacterial responses by encoding anti-CRISPR inhibitor proteins (Acr). However, the structural basis for their inhibitory actions remains largely unknown. Here, we report the crystal structure of the AcrIIA2-SpyCas9-sgRNA (single-guide RNA) complex at 3.3 ? resolution. We show that AcrIIA2 binds SpyCas9 at a position similar to the target DNA binding region. More specifically, AcrIIA2 interacts with the protospacer adjacent motif (PAM) recognition residues of Cas9, preventing target double-stranded DNA (dsDNA) detection. Thus, phage-encoded AcrIIA2 appears to act as a DNA mimic that blocks subsequent dsDNA binding by virtue of its highly acidic residues, disabling bacterial Cas9 by competing with target dsDNA binding with a binding motif distinct from AcrIIA4. Our study provides a more detailed mechanistic understanding of AcrIIA2-mediated inhibition of SpyCas9, the most widely used genome-editing tool, opening new avenues for improved regulatory precision during genome editing.

文章链接:https://www.cell.com/molecular-cell/fulltext/S1097-2765(18)30981-X#

相关报道:http://www.ibp.cas.cn/kyjz/zxdt/201901/t20190102_5224168.html

 

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