6JDX

Crystal structure of AcrIIC2 dimer in complex with partial Nme1Cas9 preprocessed with protease alpha-Chymotrypsin

6JDX の概要

• エントリーDOI: 10.2210/pdb6jdx/pdb
• 分子名称: AcrIIC2, CRISPR-associated endonuclease Cas9, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: crispr-cas9, nme1cas9, nmecas9, anti-crispr, acriic2, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Neisseria meningitidis 8013; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 37246.93

構造登録者

Cheng, Z.,Huang, X.,Sun, W.,Wang, Y. (登録日: 2019-02-02, 公開日: 2019-05-15, 最終更新日: 2023-11-22)

主引用文献

Thavalingam, A.,Cheng, Z.,Garcia, B.,Huang, X.,Shah, M.,Sun, W.,Wang, M.,Harrington, L.,Hwang, S.,Hidalgo-Reyes, Y.,Sontheimer, E.J.,Doudna, J.,Davidson, A.R.,Moraes, T.F.,Wang, Y.,Maxwell, K.L.
Inhibition of CRISPR-Cas9 ribonucleoprotein complex assembly by anti-CRISPR AcrIIC2.
Nat Commun, 10:2806-2806, 2019

PubMed 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 AcrIIC2 alone and in complex with Nme1Cas9. We demonstrate that AcrIIC2 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 AcrIIC2 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.

PubMed: 31243272
DOI: 10.1038/s41467-019-10577-3

実験手法

X-RAY DIFFRACTION (2.28 Å)