期刊
MOLECULAR CELL
卷 63, 期 5, 页码 840-851出版社
CELL PRESS
DOI: 10.1016/j.molcel.2016.07.027
关键词
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资金
- Damon Runyon Cancer Research Foundation [DRG-2218-15]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1244557] Funding Source: National Science Foundation
Bacteria employ surveillance complexes guided by CRISPR (clustered, regularly interspaced, short palindromic repeats) RNAs (crRNAs) to target foreign nucleic acids for destruction. Although most type I and type III CRISPR systems require four or more distinct proteins to form multi-subunit surveillance complexes, the type I-C systems use just three proteins to achieve crRNA maturation and double-stranded DNA target recognition. We show that each protein plays multiple functional and structural roles: Cas5c cleaves pre-crRNAs and recruits Cas7 to position the RNA guide for DNA binding and unwinding by Cas8c. Cryoelectron microscopy reconstructions of free and DNA-bound forms of the Cascade/I-C surveillance complex reveal conformational changes that enable R-loop formation with distinct positioning of each DNA strand. This streamlined type I-C system explains how CRISPR pathways can evolve compact structures that retain full functionality as RNA-guided DNA capture platforms.
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