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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)
Structures of Neisseria meningitidis Cas9 Complexes in Catalytically Poised and Anti-CRISPR-Inhibited States,Mol Cell, 24 Oct 2019
2019-10-24 | 【     】【打印】【关闭

Molecular Cell24 October, 2019,DOI:https://doi.org/10.1016/j.molcel.2019.09.025

Structures of Neisseria meningitidis Cas9 Complexes in Catalytically Poised and Anti-CRISPR-Inhibited States

Wei Sun, Jing Yang, Zhi Cheng, Nadia Amrani, Chao Liu, Kangkang Wang, Raed Ibraheim, Alireza Edraki, Xue Huang, Min Wang, Jiuyu Wang, Liang Liu, Gang Sheng, Yanhua Yang, Jizhong Lou, Erik J. Sontheimer, Yanli Wang

Summary

High-resolution Cas9 structures have yet to reveal catalytic conformations due to HNH nuclease domain positioning away from the cleavage site. Nme1Cas9 and Nme2Cas9 are compact nucleases for in vivo genome editing. Here, we report structures of meningococcal Cas9 homologs in complex with sgRNA, dsDNA, or the AcrIIC3 anti-CRISPR protein. DNA-bound structures represent an early step of target recognition, a later HNH pre-catalytic state, the HNH catalytic state, and a cleaved-target-DNA-bound state. In the HNH catalytic state of Nme1Cas9, the active site is seen poised at the scissile phosphodiester linkage of the target strand, providing a high-resolution view of the active conformation. The HNH active conformation activates the RuvC domain. Our structures explain how Nme1Cas9 and Nme2Cas9 read distinct PAM sequences and how AcrIIC3 inhibits Nme1Cas9 activity. These structures provide insights into Cas9 domain rearrangements, guide-target engagement, cleavage mechanism, and anti-CRISPR inhibition, facilitating the optimization of these genome-editing platforms.

文章链接:https://www.cell.com/molecular-cell/fulltext/S1097-2765(19)30730-0

相关报道:http://www.ibp.cas.cn/kyjz/zxdt/201910/t20191025_5412332.html

 

 

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