最新重要论文(影响因子PNAS及以上)

Inhibition of CRISPR-Cas9 ribonucleoprotein complex assembly by anti-CRISPR AcrIIC2, Nature Comm, 26 Jun 2019

发布时间:2019年06月25日

Nature Communications26 June, 2019

Inhibition of CRISPR-Cas9 ribonucleoprotein complex assembly by anti-CRISPR AcrIIC2

Annoj Thavalingam, Zhi Cheng, Bianca Garcia, Xue Huang, Megha Shah, Wei Sun, Min Wang, Lucas Harrington, Sungwon Hwang, Yurima Hidalgo-Reyes, Erik J. Sontheimer, Jennifer Doudna, Alan R. Davidson, Trevor F. Moraes, Yanli Wang & Karen L. Maxwell

Abstract

CRISPR-Cas adaptive immune systems function to protect bacteria from invasion by foreign genetic elements. The CRISPR-Cas9 system has been widely adopted as a powerful genome-editing tool, and phage-encoded inhibitors, known as anti-CRISPRs, offer a means of regulating its activity. Here, we report the crystal structures of anti-CRISPR protein AcrIIC2Nme alone and in complex with Nme1Cas9. We demonstrate that AcrIIC2Nme inhibits Cas9 through interactions with the positively charged bridge helix, thereby preventing sgRNA loading. In vivo phage plaque assays and in vitro DNA cleavage assays show that AcrIIC2Nme mediates its activity through a large electronegative surface. This work shows that anti-CRISPR activity can be mediated through the inhibition of Cas9 complex assembly.

文章链接:https://www.nature.com/articles/s41467-019-10577-3

相关报道:http://www.ibp.cas.cn/kyjz/zxdt/201907/t20190708_5336462.html

 

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