生物
机制(生物学)
劈理(地质)
DNA
多样性(政治)
计算生物学
进化生物学
遗传学
细胞生物学
古生物学
认识论
人类学
断裂(地质)
哲学
社会学
作者
Peiyu Xu,Makoto Saito,Guilhem Faure,Samantha Maguire,Samuel Chau-Duy-Tam Vo,Max E. Wilkinson,Huihui Kuang,Wei Wang,William J. Rice,Rhiannon K. Macrae,Feng Zhang
出处
期刊:Cell
[Elsevier]
日期:2024-08-28
卷期号:187 (19): 5238-5252.e20
被引量:2
标识
DOI:10.1016/j.cell.2024.07.050
摘要
Fanzor (Fz) is an ωRNA-guided endonuclease extensively found throughout the eukaryotic domain with unique gene editing potential. Here, we describe the structures of Fzs from three different organisms. We find that Fzs share a common ωRNA interaction interface, regardless of the length of the ωRNA, which varies considerably across species. The analysis also reveals Fz's mode of DNA recognition and unwinding capabilities as well as the presence of a non-canonical catalytic site. The structures demonstrate how protein conformations of Fz shift to allow the binding of double-stranded DNA to the active site within the R-loop. Mechanistically, examination of structures in different states shows that the conformation of the lid loop on the RuvC domain is controlled by the formation of the guide/DNA heteroduplex, regulating the activation of nuclease and DNA double-stranded displacement at the single cleavage site. Our findings clarify the mechanism of Fz, establishing a foundation for engineering efforts.
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