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-Structure paper
タイトル | AcrIF5 specifically targets DNA-bound CRISPR-Cas surveillance complex for inhibition. |
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ジャーナル・号・ページ | Nat Chem Biol, Vol. 18, Issue 6, Page 670-677, Year 2022 |
掲載日 | 2022年3月17日 |
著者 | Yongchao Xie / Laixing Zhang / Zhengyu Gao / Peipei Yin / Hao Wang / Hang Li / Zeliang Chen / Yi Zhang / Maojun Yang / Yue Feng / |
PubMed 要旨 | CRISPR-Cas systems are prokaryotic antiviral systems, and phages use anti-CRISPR proteins (Acrs) to inactivate these systems. Here we present structural and functional analyses of AcrIF5, exploring ...CRISPR-Cas systems are prokaryotic antiviral systems, and phages use anti-CRISPR proteins (Acrs) to inactivate these systems. Here we present structural and functional analyses of AcrIF5, exploring its unique anti-CRISPR mechanism. AcrIF5 shows binding specificity only for the target DNA-bound form of the crRNA-guided surveillance (Csy) complex, but not the apo Csy complex from the type I-F CRISPR-Cas system. We solved the structure of the Csy-dsDNA-AcrIF5 complex, revealing that the conformational changes of the Csy complex caused by dsDNA binding dictate the binding specificity for the Csy-dsDNA complex by AcrIF5. Mechanistically, five AcrIF5 molecules bind one Csy-dsDNA complex, which destabilizes the helical bundle domain of Cas8f, thus preventing subsequent Cas2/3 recruitment. AcrIF5 exists in symbiosis with AcrIF3, which blocks Cas2/3 recruitment. This attack on the recruitment event stands in contrast to the conventional mechanisms of blocking binding of target DNA. Overall, our study reveals an unprecedented mechanism of CRISPR-Cas inhibition by AcrIF5. |
リンク | Nat Chem Biol / PubMed:35301482 |
手法 | EM (単粒子) / X線回折 |
解像度 | 3.2 - 3.52 Å |
構造データ | EMDB-31265, PDB-7eqg: PDB-7f45: |
由来 |
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キーワード | IMMUNE SYSTEM/RNA/DNA / complex / inhibitor / IMMUNE SYSTEM / IMMUNE SYSTEM-RNA-DNA complex / monomer / mixed alpha-beta structure |