反式激活crRNA
清脆的
生物
碱基对
核糖核酸
Cas9
核酸酶
遗传学
回文
DNA
质粒
计算生物学
核酸
基因
作者
Blake Wiedenheft,Gabriel C. Lander,Keming Zhou,Matthijs M. Jore,Stan J. J. Brouns,John van der Oost,Jennifer A. Doudna,Eva Nogales
出处
期刊:Nature
[Springer Nature]
日期:2011-09-21
卷期号:477 (7365): 486-489
被引量:346
摘要
Bacteria and archaea acquire resistance to viruses and plasmids by integrating short fragments of foreign DNA into clustered regularly interspaced short palindromic repeats (CRISPRs). These repetitive loci maintain a genetic record of all prior encounters with foreign transgressors. CRISPRs are transcribed and the long primary transcript is processed into a library of short CRISPR-derived RNAs (crRNAs) that contain a unique sequence complementary to a foreign nucleic-acid challenger. In Escherichia coli, crRNAs are incorporated into a multisubunit surveillance complex called Cascade (CRISPR-associated complex for antiviral defence), which is required for protection against bacteriophages. Here we use cryo-electron microscopy to determine the subnanometre structures of Cascade before and after binding to a target sequence. These structures reveal a sea-horse-shaped architecture in which the crRNA is displayed along a helical arrangement of protein subunits that protect the crRNA from degradation while maintaining its availability for base pairing. Cascade engages invading nucleic acids through high-affinity base-pairing interactions near the 5' end of the crRNA. Base pairing extends along the crRNA, resulting in a series of short helical segments that trigger a concerted conformational change. This conformational rearrangement may serve as a signal that recruits a trans-acting nuclease (Cas3) for destruction of invading nucleic-acid sequences.
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